The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results show... The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.展开更多
BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE： To observe the effects o...BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE： To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN： A randomized controlled tria SETTING： Department of Human Anatomy and Histological Embryology, School of Medicine, Xi＇an Jiaotong University. MATERIALS： Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi＇an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd （Lot Number： 2004051106, Specification： 2 mL/piece）. METHODS ： The experiments were carried out in School of Medicine of Xi＇an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method： sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES ： The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS： Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [（23.92±2.21）, （41.84±3.74）, （39.50 ±3.80）, （31.38_±3.72）, （61.60±3.61） s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [（36.27±3.42） %, （35.84±2.54）%, （38.43±3.08）%, （36.51±1.96）%, （22.24±3.46）%; （11 ±1 ）, （10±1）, （8_±1）, （8±1）, （4±1） times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral （left） parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [（98±8）, （65±5）, （53±6）, （57±6）, （37±6）/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS:...OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS: Nine-month-old female mice with senescence-accelerated mouse prone 8(SAMP8)were divided into three groups: the disease model,EA-Guanyuan and EA-Sanyinjiao groups. Concurrently, 9-month old female mice with senescence-accelerated mouse resistance 1(SAMR1)were set as the control model group. The two treatment groups were given the same pattern of EA stimulation. Gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent assay to determinethe HPO axis function level. Spatial learning and memory were assessed by the Morris Water Maze(MWM) test.RESULTS:(a) HPO axis: compared with the control model group, the disease model group displayed a decrease in E2 levels(P < 0.01), and an increase in Gn RH, LH and FSH levels(P < 0.01). E2 levels were increased in EA treatment groups compared with the disease model group(P < 0.05). In contrast,Gn RH and LH and FSH levels were reduced(P <0.05). EA-Sanyinjiao group was superior than EA-Guanyuan group on increasing E2 and declining Gn RH levels(P < 0.01).(b) The MWM test demonstrated that the response latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared with the disease model group(P <0.05), whereas the EA-Guanyuan treatment group showed no significant difference.CONCLUSION: EA can regulate hormone(E2, FSH,LH, Gn RH) levels in the HPO axis and the spatial learning and memory ability in female SAMP8 mice. Moreover, this effect may have been more pronounced in the EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism of the EA-induced changes may be related to gonadal hormone shifts in the HPO axis, followed by an improvement in spatial learning and memory.展开更多
OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with ...OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1· d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real- time quantitative PCR and spectrophotometry,respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry. RESULTS: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose- induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression. CONCLUSION: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.展开更多
The detrimental effects of constant hyperglycemia on neural function have been quantitatively and qualitatively evaluated in the setting of diabetes mellitus. Some of the hallmark features of diabetic encephalopathy (...The detrimental effects of constant hyperglycemia on neural function have been quantitatively and qualitatively evaluated in the setting of diabetes mellitus. Some of the hallmark features of diabetic encephalopathy (DE) are impaired synaptic adaptation and diminished spatial learning capacity. Chronic and progressive cognitive dysfunction, perpetuated by several positive feedback mechanisms in diabetic subjects, facilitates the development of early-onset dementia and Alzheimer’s disease. Despite the numerous clinical manifestations of DE having been described in detail and their pathophysiological substrate having been elucidated in both type 1 and type 2 diabetes mellitus, an effective therapeutic approach is yet to be proposed. Therefore, the aim of this review is to summarize the growing body of evidence concerning the effect of current antidiabetic treatment options on diabetic and non-DE.展开更多
BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them ...BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.展开更多
Objective:We aimed to investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+、GLU、Ab1-42 in the brain tissue and peripheral blood.Meth...Objective:We aimed to investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+、GLU、Ab1-42 in the brain tissue and peripheral blood.Methods:Mice were randomly assigned to sham operation,Aβ25-35,Aβ25-35+Ost-L,Aβ25-35+Ost-M,and Aβ25-35+Ost-H group.Water maze test was performed to assessing spatial learning ability of mice.It is determined that the MDA level and the activity of SOD in the brain tissue of mice in each group by colorimetry.The GLU kit and Ca2+kit were used to detect the GLU,Ca2+in tissue and serum.Elisa was used to detect the expression of Aβ1-42 in the hippocampus and serum of mice.HE staining and silver staining were used to detect neuron apoptosis and pathological changes in brain slices.Results:①Effects of osthole on learning and memory:With the increase of training day,the escape latencies continuously reduced in each experimental group,the escape latencies of the model group was longer on the 1st,2nd,3rd,and 5th days than the normal group,the difference was statistically significant(day 3,4:P<0.05,day 5:P<0.01);compared with the model group,the escaping latency on the fifth day of the OST low-medium high-dose group was significantly shortened,which was statistically significant(P<0.05).②Effects on oxidative stresspathway:the SOD activity of AD mice in the hippocampus model group was lower than that in the normal group,which was statistically significant(P<0.05);The SOD activity in the OST group was higher than that in the model group,which was statistically significant(P<0.05).The MDA content in the model group was significantly higher than that in the normal group(P<0.05).The MDA content in the OST high-dose group was lower than that in the model group,which was statistically significant(P<0.05).③Effects of GLU levels on neurotransmitters:the results of the detection of GLU in cortical area and GLU in serum of AD mice in OST dose groups showed that serum GLU levels in the model group were significantly lower than those in the sham group,which was statistically significant(P<0.05).GLU levels in the cortical area were also significantly higher than those in the sham group,which was statistically significant(P<0.05).Compared with the model group,GLU levels in the OST administration group were significantly downregulated.Among the serum,the effect of medium dose group was obvious.Although there was a trend of down-regulation in the cortical administration group,there was no statistical significance.④Changes in Ca2+concentration in the brain;Detection of intracellular Ca ion concentration in AD mice by OST doses showed that,compared with the sham group,the model group was significantly upregulated in cortical Ca2+levels.There was no statistical difference in the administration group.Compared with the model group,the concentration of Ca2+in the OST-H group significantly decreased.⑤Effect on levels of Ab1-42 in hippocampus and serum:model group had significantly higher Ab1-42 levels in hippocampus than in sham operation group,which was statistically significant(P<0.05).Ab1-42 in serum was also significantly upregulated compared to the sham group,which was statistically significant(P<0.05).Compared with the model group,the levels of Aβ1-42 in the OST administration group were significantly down-regulated,with the lower and middle doses in the hippocampus being more significant,while the serum was more pronounced at lower doses.⑥Silver staining to detect the tangles of hippocampal neurons:Neuron tangles in the hippocampal CA1 region showed a dark brown-yellow granule distribution in the nuclei of the model group(positive expression).Nerve cell body and dendrites,axons are black or black red,background light yellow.Compared with the model group,the administration group has improved significantly.Conclusion:OST improves spatial learning and memory of dementia model mice injected with Ab25-35 in both hippocampus.Experimental studies have shown that OST has different degrees of regulation on neuronal apoptosis,Ca2+/GLU/oxidative stress and other pathways,and it plays a role in improving multiple AD pathological changes and delaying the pathogenesis of neurodegenerative diseases.展开更多
Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this stu...Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this study, we investigate whether developmental exposure to Malathion could impair spatial learning and recognition memory in male rats. Animals exposed by intragastric route, from in utero to young adult stage, to incremental doses of Malathion dissolved in corn oil;100, 200 and 300 mg/kg of body weight, and one control group are given corn oil. Then, cognitive and behaveioral abilities are assessed using Barnes maze and object recognition memory task. Malathion administration at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. Rats exposed to 200 mg/kg make a significant working memory error, and require more time to find an escape box during the initial training phase of Barnes maze. However, fewer errors are made in rats exposed to 100 mg/kg. For reversal learning task, the high dose group shows great deficits in spatial strategy to locate the new position of the box. With respect to recognition task, both dose 100 and 200 mg/kg impair significant short-term (2 h after habituation phase) object recognition memory, but long-term (24 h after habituation phase) recognition memory is intact in high dose group. The current study also reveals that all treatments induce high significant neocortex acetylcholinesterase (AChE) activity inhibition, but 100 mg/kg dose is not sufficient to disrupt great hippocampal activity alteration. These results suggest that developmental exposure to Malathion, despite low toxicity described, may induce late-emerging spatial learning and recognition memorialterations. Moreover, Cortical and hippocampal area that support strongly these behaviors remain sensitive to incremental doses of Malathion.展开更多
Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generation...Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain, DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze （MWM） was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain, The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Condusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.展开更多
Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. Th...Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats. Thirty-five male Wistar rats were intraperitoneally injected with 0, 50, 100, 200 and 400 mg/kg butternut squash extract once daily for 2 months. After the last administration, rat＇s spatial memory was studied using the Morris water maze. Finally, rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies. The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats, and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls. These findings suggest that butternut squash extract improves the learning and memory abilities of male rats, and increases the proliferation of dentate gyrus cells.展开更多
A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown abou...A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.展开更多
Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and be...Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.展开更多
The active components associated with the bio-designer drugs known variously as “Spice” or “K2” have rapidly gained in popularity among recreational users, forcing the United States Drug Enforcement Administration...The active components associated with the bio-designer drugs known variously as “Spice” or “K2” have rapidly gained in popularity among recreational users, forcing the United States Drug Enforcement Administration to classify these compounds as Schedule I drugs in the Spring of 2011. However, although there is some information about many of the synthetic cannabinoids used in Spice products, little is known about the consequences of the main constituent, (1-pentyl-3-(1-naphthoyl)indole;JWH-018), on neuropsychological development or behavior. In the present experiment, adolescent rats were given repeated injections of either saline or 100 μg/kg of JWH-018. Once the animals were 75 days of age, they were trained using tasks with spatial components of various levels of difficulty and a spatial learning set task. On early trials with water maze tasks of varying difficulty, the JWH-018 treated rats were impaired relative to controls. However, by the end of each phase of testing, drug and control animals were comparable, although on probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a learning set task, suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this potent cannabinoid CB1 receptor agonist during adolescence is capable of producing a variety of subtle changes affecting spatial learning and memory performance in adulthood, well after the drug exposure period.展开更多
On aging, spatial memory declines to some degree in both, rodents and humans. It is unknown, however, whether aging brings about a decline of encoding and retrieval of spatial information in parallel. The present stud...On aging, spatial memory declines to some degree in both, rodents and humans. It is unknown, however, whether aging brings about a decline of encoding and retrieval of spatial information in parallel. The present study examined spatial encoding and retrieval in male CD-1 mice at 4, 9, and 12 months of age in a complex dry-land maze. The total time to reach the goal zone was age-dependent favoring mice at 4 months of age. We showed previously that moving time represents encoding of spatial information and resting time represents recall of previously learned spatial information. The average moving time decreased from 69.8 ± 5.3 s (mean ± SEM), 69.7 ± 8.0 s, and 78.9 ± 4.9 s to 17.0 ± 2.3 s (p < 0.001 ), 24.7 ± 2.7 s (p < 0.001), and 31.0 ± 3.5 s (p < 0.001) at 4, 9, and 12 months of age, respectively. The average resting time decreased from 34.9 ± 5.6 s, 22.2 ± 4.2 s, and 41.7 ± 5.3 s to 3.6 ± 1.2 s (p < 0.001), 5.3 ± 1.8 s (p = 0.009), and 22.7 ± 4.9 s (p = 0.007) at 4, 9, and 12 months of age, respectively. We conclude that age-related deficits of spatial memory in mice manifest with an encoding deficit prior to a retrieval deficit.展开更多
BACKGROUND： Studies have demonstrated that lead exposure can result in cognitive dysfunction and behavior disorders. However, lead exposure impairments vary under different experimental conditions. OBJECTIVE： To det...BACKGROUND： Studies have demonstrated that lead exposure can result in cognitive dysfunction and behavior disorders. However, lead exposure impairments vary under different experimental conditions. OBJECTIVE： To detect changes in spatial learning and memory following low-level lead exposure in rats, in Morris water maze test under the same experimental condition used to analyze lead exposure effects on various memory types and learning processes. DESIGN AND SETTING： The experiment was conducted at the Animal Laboratory, Institute of Psychology, Chinese Academy of Science between February 2005 and March 2006. One-way analysis of variance （ANOVA） and behavioral observations were performed. MATERIALS： Sixteen male, healthy, adult, Sprague Dawley rats were randomized into normal con-trol and lead exposure groups （n = 8）. METHODS： Rats in the normal control group were fed distilled water, and those in the lead exposure group were fed 250 mL of 0.05% lead acetate once per day. At day 28, all rats performed the Morris water maze test, consisting of four phases： space navigation, probe test, working memory test, and visual cue test. MAIN OUTCOME MEASURES： Place navigation in the Morris water maze was used to evaluate spatial learning and memory, probe trials for spatial reference memory, working memory test for spatial working memory, and visual cue test for non-spatial cognitive function. Perkin-Elmer Model 300 Atomic Absorption Spectrometer was utilized to determine blood lead levels in rats. RESULTS： （1） In the working memory test, the time to reach the platform remained unchanged between the control and lead exposure groups （F（1,1） = 0.007, P = 0.935）. A visible decrease in escape latencies was observed in each group （P = 0.028）. However, there was no significant difference between the two groups （F（1,1） = 1.869, P = 0.193）. The working memory probe test demonstrated no change between the two groups in the time spent in the target quadrant during the working memory probe test （F（1,1） = 1.869, P = 0.193）. However, by day 4, differences were observed in the working memory test （P 〈 0.01）. （2） Multivariate repetitive measure and ANOVA in place navigation presented no significant difference between the two groups （F（1,1） = 0.579, P = 0.459）. （3） Spatial probe test demonstrated that the time to reach the platform was significantly different between the two groups （F（1,1） = 4.587, P = 0.048）, and one-way ANOVA showed no significant difference in swimming speed between the two groups （F（1,1） = 1.528, P = 0.237）. （4） In the visual cue test, all rats reached the platform within 15 seconds, with no significant difference （F（1,1） = 0.579, P = 0.459）. （5） During experimentation, all rats increased in body mass, but there was no difference between the two groups （F（1,1） = 0.05, P = 0.943）. At day 28 of 0.05% lead exposure, the blood lead level was 29.72 μg/L in the lead exposure group and 5.86 μg/L in the control group （P 〈 0.01）. CONCLUSION： The present results revealed low-level lead exposure significantly impaired spatial reference memory and spatial working memory, but had no effect on spatial learning.展开更多
Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 ...Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 Wistar rats were randomly divided into four groups(n=12)of blank control,low dose,medium dose and high dose.The blank control group was gavaged daily saline,and the other three dose groups were given daily gavage AlCl3 aqueous solution at three doses of 25 mg/kg,50 mg/kg,and 100 mg/kg to create a rat model of cognitive impairment for three months.The water maze(MWM)positioning navigation experiment was used to record the time t(s),namely,the incubation period,on the platform of rats,and the incubation period of each group was used to determine whether the rats in the infected group had learning and memory impairment.Hematoxylin-eosin(HE)and Nissl stains observed the pathological changes of nerve cells in the hippocampus of the four groups.Western blot detected the protein expression levels of RHOA and cranial neurotrophic factor(BDNF)in fresh rat hippocampal tissues.RT-qPCR detected the mRNA expression of miR-9-5p,RHOA,and BDNF in rat hippocampal tissues.Results:The results of Morris water maze positioning navigation test showed that the incubation period of each group was calculated on the 1st,3rd and 5th days of the experiment,and the motor incubation period of the infected group was higher than that of the control group.The results of HE staining showed that the rat nerve cells in the control group were morphologically intact,the staining was clear,the nucleus was clearly visible,and the edge of the cell membrane was sharp.The rat neurons in the infected group were damaged to varying degrees,the nucleus gradually dissolved,the cytoplasmic staining became deeper,the edges of the cell membrane were blurred and disordered,and the cells were deformed and arranged disordered.The results of Nissl staining showed that the well-stained Nissl body particles were visible in the nerve cells of rats in the control group,and the dissipation of Nissl bodies in the nerve cells of the infected group was reduced,and the staining was shallow.The results of RT-qPCR showed that compared with the control group,the mRNA expression of miR-9-5p and BDNF was decreased in the infected group,and the mRNA expression of RHOA was increased(P<0.05 or P<0.001).The Western blot results showed that compared with the control group,the relative expression of BDNF in the three infected groups was decreased,and the relative expression of RHOA increased(P<0.05).Conclusion:In aluminum-induced cognitive impairment,miR-9-5p is downregulated and RHOA is upregulatd.展开更多
Ivane S. Beritashvili’s doctrine of image-driven behavior was established in the late 1920s and finally extended in his books in English (1965;1971). It bears a strong resemblance to the concepts of purposive behavio...Ivane S. Beritashvili’s doctrine of image-driven behavior was established in the late 1920s and finally extended in his books in English (1965;1971). It bears a strong resemblance to the concepts of purposive behavior and “cognitive maps” developed in parallel by Edward C. Tolman (1932;1948) and significantly anticipated respective modern concepts. John O’Keefe and his disciples May-Britt Moser and Edvard I. Moser received the Nobel Prize in 2014 for their discoveries of cells that constitute a navigation system in the brain. The latter fact brings us to the pioneers of the study of the spatial orientation of animals that figuratively speaking, provided the giant’s shoulders on which O’Keefe and the Mosers stood to receive their award. Beritashvili and Tolman upheld the holistic and goal-directed nature of spatial behavior. A major contribution of Beritashvili to the science of animal behavior was the demonstration of the universality of learning following a single presentation of an object vitally important to the animal: either a food object or a noxious signal. Beritashvili showed that such “image-driven” behavior has a strong spatial component, i.e., the image is projected into a definite point in space. Thus, he came to maintain that there is a class of behavior that is image-driven that does not require a repetition of associations. Tolman made several significant contributions to the field of experimental psychology. He thought of learning as developing from bits of knowledge and cognitions about the environment and how the organism relates to it. He examined the role that reinforcement plays in the way that rats learn their way through complex mazes. These experiments eventually led to the theory of latent learning which describes learning that occurs in the absence of an obvious reward. Tolman also strongly advocated the theory that rats learn the place where they have been rewarded rather than the particular movements required to get there. To a great extent, Tolman’s work determined the direction of American psychology in the 1930s-1950s. The contribution of Beritashvili and Tolman, thus, is the groundwork of modern studies of spatial cognitive processes in human and nonhuman animals.展开更多
Background： The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodont...Background： The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San （DSS） is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. Methods： A total of 36 rats were randornly divided into three groups： （ 1 ） Sham group （n = 12）, rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment： （2） experimental tooth movement （ETM） group （n - 12）, rats received saline treatment and ETM： （3） DSS ＋ ETM （DETM） group （n = 12）, rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Monis water maze test was evaluated： immunofluorescent histochemistry was used to identity astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. Results： Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased cornpared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus （DG）. Conclusions： Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG ofhippocampus in the ETM group rats may be related with the decline of the ability of learning and rnernory. The ability to change the synaptic plasticity in hippocarnpus after DSS administration may be correlated with the alleviation of impairment of learn and memory atter ETM treatment.展开更多
Rho-associated kinases(ROCKs)are serinethreonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton.Two ROCK isoforms(ROCK1 and ROCK2)are expressed in the mamma...Rho-associated kinases(ROCKs)are serinethreonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton.Two ROCK isoforms(ROCK1 and ROCK2)are expressed in the mammalian central nervous system.Although ROCK activity has been implicated in synapse formation,whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear.Here,we used a genetic approach to address this long-standing question.Both Rock1^+/- and Rock2^+/- mice had impaired glutamatergic transmission,reduced spine density,and fewer excitatory synapses in hippocampal CA1 pyramidal neurons.In addition,both Rockl^+/- and Rock2^+/- mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests.However,the spine morphology of CA1 pyramidal neurons was altered only in Rock2^+/- but not Rock1^+/- mice.In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time.Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.展开更多
文摘 The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.
基金the National Natural Science Foundation of China, No. 30170300 30300109
文摘BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE： To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN： A randomized controlled tria SETTING： Department of Human Anatomy and Histological Embryology, School of Medicine, Xi＇an Jiaotong University. MATERIALS： Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi＇an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd （Lot Number： 2004051106, Specification： 2 mL/piece）. METHODS ： The experiments were carried out in School of Medicine of Xi＇an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method： sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES ： The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS： Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [（23.92±2.21）, （41.84±3.74）, （39.50 ±3.80）, （31.38_±3.72）, （61.60±3.61） s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [（36.27±3.42） %, （35.84±2.54）%, （38.43±3.08）%, （36.51±1.96）%, （22.24±3.46）%; （11 ±1 ）, （10±1）, （8_±1）, （8±1）, （4±1） times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral （left） parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [（98±8）, （65±5）, （53±6）, （57±6）, （37±6）/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金the National Science Foundation of China(the Experimental Research on Acupuncture for Prevention and Treatment Alzheimer's Disease Based on the Adjustment Imbalances of NIM,No.81072768)
文摘OBJECTIVE: To investigate the effects of electroacupuncture(EA) at the Guanyuan(CV 4) or Sanyinjiao(SP 6) acupoints on the hypothalamus-pituitary-ovary(HPO) axis and spatial learning and memory in female mice.METHODS: Nine-month-old female mice with senescence-accelerated mouse prone 8(SAMP8)were divided into three groups: the disease model,EA-Guanyuan and EA-Sanyinjiao groups. Concurrently, 9-month old female mice with senescence-accelerated mouse resistance 1(SAMR1)were set as the control model group. The two treatment groups were given the same pattern of EA stimulation. Gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone(FSH) and Serum estradiol levels in the Hypothalamus-pituitary-ovary axis were assessed by enzyme-linked immunosorbent assay to determinethe HPO axis function level. Spatial learning and memory were assessed by the Morris Water Maze(MWM) test.RESULTS:(a) HPO axis: compared with the control model group, the disease model group displayed a decrease in E2 levels(P < 0.01), and an increase in Gn RH, LH and FSH levels(P < 0.01). E2 levels were increased in EA treatment groups compared with the disease model group(P < 0.05). In contrast,Gn RH and LH and FSH levels were reduced(P <0.05). EA-Sanyinjiao group was superior than EA-Guanyuan group on increasing E2 and declining Gn RH levels(P < 0.01).(b) The MWM test demonstrated that the response latency in the EA-Sanyinjiao treatment group declined from day 2 to day5 compared with the disease model group(P <0.05), whereas the EA-Guanyuan treatment group showed no significant difference.CONCLUSION: EA can regulate hormone(E2, FSH,LH, Gn RH) levels in the HPO axis and the spatial learning and memory ability in female SAMP8 mice. Moreover, this effect may have been more pronounced in the EA-Sanyinjiao group than the EA-Guanyuan group. The underlying mechanism of the EA-induced changes may be related to gonadal hormone shifts in the HPO axis, followed by an improvement in spatial learning and memory.
基金Supported by the by the Natural Science Foundation of Henan:Study of Eclipta Prostrata Extract in Aging(2020-ZZJH-339,17A180010)
文摘OBJECTIVE: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats. METHODS: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1· d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real- time quantitative PCR and spectrophotometry,respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry. RESULTS: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose- induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression. CONCLUSION: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.
文摘The detrimental effects of constant hyperglycemia on neural function have been quantitatively and qualitatively evaluated in the setting of diabetes mellitus. Some of the hallmark features of diabetic encephalopathy (DE) are impaired synaptic adaptation and diminished spatial learning capacity. Chronic and progressive cognitive dysfunction, perpetuated by several positive feedback mechanisms in diabetic subjects, facilitates the development of early-onset dementia and Alzheimer’s disease. Despite the numerous clinical manifestations of DE having been described in detail and their pathophysiological substrate having been elucidated in both type 1 and type 2 diabetes mellitus, an effective therapeutic approach is yet to be proposed. Therefore, the aim of this review is to summarize the growing body of evidence concerning the effect of current antidiabetic treatment options on diabetic and non-DE.
文摘BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.
文摘Objective:We aimed to investigate the effects of osthole on learning and memory impairment of AD mice induced by injection of Aβ25-35 and the content of Ca2+、GLU、Ab1-42 in the brain tissue and peripheral blood.Methods:Mice were randomly assigned to sham operation,Aβ25-35,Aβ25-35+Ost-L,Aβ25-35+Ost-M,and Aβ25-35+Ost-H group.Water maze test was performed to assessing spatial learning ability of mice.It is determined that the MDA level and the activity of SOD in the brain tissue of mice in each group by colorimetry.The GLU kit and Ca2+kit were used to detect the GLU,Ca2+in tissue and serum.Elisa was used to detect the expression of Aβ1-42 in the hippocampus and serum of mice.HE staining and silver staining were used to detect neuron apoptosis and pathological changes in brain slices.Results:①Effects of osthole on learning and memory:With the increase of training day,the escape latencies continuously reduced in each experimental group,the escape latencies of the model group was longer on the 1st,2nd,3rd,and 5th days than the normal group,the difference was statistically significant(day 3,4:P<0.05,day 5:P<0.01);compared with the model group,the escaping latency on the fifth day of the OST low-medium high-dose group was significantly shortened,which was statistically significant(P<0.05).②Effects on oxidative stresspathway:the SOD activity of AD mice in the hippocampus model group was lower than that in the normal group,which was statistically significant(P<0.05);The SOD activity in the OST group was higher than that in the model group,which was statistically significant(P<0.05).The MDA content in the model group was significantly higher than that in the normal group(P<0.05).The MDA content in the OST high-dose group was lower than that in the model group,which was statistically significant(P<0.05).③Effects of GLU levels on neurotransmitters:the results of the detection of GLU in cortical area and GLU in serum of AD mice in OST dose groups showed that serum GLU levels in the model group were significantly lower than those in the sham group,which was statistically significant(P<0.05).GLU levels in the cortical area were also significantly higher than those in the sham group,which was statistically significant(P<0.05).Compared with the model group,GLU levels in the OST administration group were significantly downregulated.Among the serum,the effect of medium dose group was obvious.Although there was a trend of down-regulation in the cortical administration group,there was no statistical significance.④Changes in Ca2+concentration in the brain;Detection of intracellular Ca ion concentration in AD mice by OST doses showed that,compared with the sham group,the model group was significantly upregulated in cortical Ca2+levels.There was no statistical difference in the administration group.Compared with the model group,the concentration of Ca2+in the OST-H group significantly decreased.⑤Effect on levels of Ab1-42 in hippocampus and serum:model group had significantly higher Ab1-42 levels in hippocampus than in sham operation group,which was statistically significant(P<0.05).Ab1-42 in serum was also significantly upregulated compared to the sham group,which was statistically significant(P<0.05).Compared with the model group,the levels of Aβ1-42 in the OST administration group were significantly down-regulated,with the lower and middle doses in the hippocampus being more significant,while the serum was more pronounced at lower doses.⑥Silver staining to detect the tangles of hippocampal neurons:Neuron tangles in the hippocampal CA1 region showed a dark brown-yellow granule distribution in the nuclei of the model group(positive expression).Nerve cell body and dendrites,axons are black or black red,background light yellow.Compared with the model group,the administration group has improved significantly.Conclusion:OST improves spatial learning and memory of dementia model mice injected with Ab25-35 in both hippocampus.Experimental studies have shown that OST has different degrees of regulation on neuronal apoptosis,Ca2+/GLU/oxidative stress and other pathways,and it plays a role in improving multiple AD pathological changes and delaying the pathogenesis of neurodegenerative diseases.
文摘Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this study, we investigate whether developmental exposure to Malathion could impair spatial learning and recognition memory in male rats. Animals exposed by intragastric route, from in utero to young adult stage, to incremental doses of Malathion dissolved in corn oil;100, 200 and 300 mg/kg of body weight, and one control group are given corn oil. Then, cognitive and behaveioral abilities are assessed using Barnes maze and object recognition memory task. Malathion administration at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. Rats exposed to 200 mg/kg make a significant working memory error, and require more time to find an escape box during the initial training phase of Barnes maze. However, fewer errors are made in rats exposed to 100 mg/kg. For reversal learning task, the high dose group shows great deficits in spatial strategy to locate the new position of the box. With respect to recognition task, both dose 100 and 200 mg/kg impair significant short-term (2 h after habituation phase) object recognition memory, but long-term (24 h after habituation phase) recognition memory is intact in high dose group. The current study also reveals that all treatments induce high significant neocortex acetylcholinesterase (AChE) activity inhibition, but 100 mg/kg dose is not sufficient to disrupt great hippocampal activity alteration. These results suggest that developmental exposure to Malathion, despite low toxicity described, may induce late-emerging spatial learning and recognition memorialterations. Moreover, Cortical and hippocampal area that support strongly these behaviors remain sensitive to incremental doses of Malathion.
文摘Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain, DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze （MWM） was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain, The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Condusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.
基金a grant from the Research Institute for Islamic and Complementary Medicine (RICM),Tehran University of Medical Sciences,No. p26/m/t/1088
文摘Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats. Thirty-five male Wistar rats were intraperitoneally injected with 0, 50, 100, 200 and 400 mg/kg butternut squash extract once daily for 2 months. After the last administration, rat＇s spatial memory was studied using the Morris water maze. Finally, rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies. The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats, and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls. These findings suggest that butternut squash extract improves the learning and memory abilities of male rats, and increases the proliferation of dentate gyrus cells.
文摘A drug of abuse, Foxy or Methoxy Foxy gained popularity among recreational users as an alternative to MDMA (Ecstasy). Considerable research into the consequences of MDMA use is available, yet much remains unknown about the neurobiological consequences of Foxy use. In addition, research into the long-term neuropsychological repercussions associated with these two compounds remains incomplete. The goal of the present research was to explore the effects of MDMA or Foxy on cognitive processes associated with adolescent exposure considered over much of the lifespan. Here we investigated whether the reported effects following adolescent exposure resolved in early adulthood or continued throughout life. The protocol involved repeated doses of either MDMA or Foxy during the period defined as mid-adolescence (postnatal days 34 - 46) in rats, followed by the use of four series of learning and memory tasks repeated at different points in the rodent lifespan. At four time points in adulthood, the animals were trained and tested on a on a series of spatial and non-spatial memory tasks designed to assess the impact and severity of Foxy and MDMA. Oddly, MDMA-treated rats were impaired on a step down passive avoidance task. The performance of the drug-treated rats was markedly inferior to that of the control animals on more demanding water maze tasks, with some results suggesting a lack of flexibility in adapting to changing task demands. MDMA rats were the most impaired. While some persistent cognitive deficits were found, no significant group differences in serotonin or dopamine levels were found in any of the measured regions of the brain changes, cortical or subcortical. These results provide evidence for compromised neurocognition that continues long after drug exposure in the absence of any discernable changes in neurotransmitter levels. Several possible physiological and neurochemical mechanisms associated with these compounds requiring further study are also outlined.
文摘Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.
文摘The active components associated with the bio-designer drugs known variously as “Spice” or “K2” have rapidly gained in popularity among recreational users, forcing the United States Drug Enforcement Administration to classify these compounds as Schedule I drugs in the Spring of 2011. However, although there is some information about many of the synthetic cannabinoids used in Spice products, little is known about the consequences of the main constituent, (1-pentyl-3-(1-naphthoyl)indole;JWH-018), on neuropsychological development or behavior. In the present experiment, adolescent rats were given repeated injections of either saline or 100 μg/kg of JWH-018. Once the animals were 75 days of age, they were trained using tasks with spatial components of various levels of difficulty and a spatial learning set task. On early trials with water maze tasks of varying difficulty, the JWH-018 treated rats were impaired relative to controls. However, by the end of each phase of testing, drug and control animals were comparable, although on probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a learning set task, suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this potent cannabinoid CB1 receptor agonist during adolescence is capable of producing a variety of subtle changes affecting spatial learning and memory performance in adulthood, well after the drug exposure period.
文摘On aging, spatial memory declines to some degree in both, rodents and humans. It is unknown, however, whether aging brings about a decline of encoding and retrieval of spatial information in parallel. The present study examined spatial encoding and retrieval in male CD-1 mice at 4, 9, and 12 months of age in a complex dry-land maze. The total time to reach the goal zone was age-dependent favoring mice at 4 months of age. We showed previously that moving time represents encoding of spatial information and resting time represents recall of previously learned spatial information. The average moving time decreased from 69.8 ± 5.3 s (mean ± SEM), 69.7 ± 8.0 s, and 78.9 ± 4.9 s to 17.0 ± 2.3 s (p < 0.001 ), 24.7 ± 2.7 s (p < 0.001), and 31.0 ± 3.5 s (p < 0.001) at 4, 9, and 12 months of age, respectively. The average resting time decreased from 34.9 ± 5.6 s, 22.2 ± 4.2 s, and 41.7 ± 5.3 s to 3.6 ± 1.2 s (p < 0.001), 5.3 ± 1.8 s (p = 0.009), and 22.7 ± 4.9 s (p = 0.007) at 4, 9, and 12 months of age, respectively. We conclude that age-related deficits of spatial memory in mice manifest with an encoding deficit prior to a retrieval deficit.
文摘BACKGROUND： Studies have demonstrated that lead exposure can result in cognitive dysfunction and behavior disorders. However, lead exposure impairments vary under different experimental conditions. OBJECTIVE： To detect changes in spatial learning and memory following low-level lead exposure in rats, in Morris water maze test under the same experimental condition used to analyze lead exposure effects on various memory types and learning processes. DESIGN AND SETTING： The experiment was conducted at the Animal Laboratory, Institute of Psychology, Chinese Academy of Science between February 2005 and March 2006. One-way analysis of variance （ANOVA） and behavioral observations were performed. MATERIALS： Sixteen male, healthy, adult, Sprague Dawley rats were randomized into normal con-trol and lead exposure groups （n = 8）. METHODS： Rats in the normal control group were fed distilled water, and those in the lead exposure group were fed 250 mL of 0.05% lead acetate once per day. At day 28, all rats performed the Morris water maze test, consisting of four phases： space navigation, probe test, working memory test, and visual cue test. MAIN OUTCOME MEASURES： Place navigation in the Morris water maze was used to evaluate spatial learning and memory, probe trials for spatial reference memory, working memory test for spatial working memory, and visual cue test for non-spatial cognitive function. Perkin-Elmer Model 300 Atomic Absorption Spectrometer was utilized to determine blood lead levels in rats. RESULTS： （1） In the working memory test, the time to reach the platform remained unchanged between the control and lead exposure groups （F（1,1） = 0.007, P = 0.935）. A visible decrease in escape latencies was observed in each group （P = 0.028）. However, there was no significant difference between the two groups （F（1,1） = 1.869, P = 0.193）. The working memory probe test demonstrated no change between the two groups in the time spent in the target quadrant during the working memory probe test （F（1,1） = 1.869, P = 0.193）. However, by day 4, differences were observed in the working memory test （P 〈 0.01）. （2） Multivariate repetitive measure and ANOVA in place navigation presented no significant difference between the two groups （F（1,1） = 0.579, P = 0.459）. （3） Spatial probe test demonstrated that the time to reach the platform was significantly different between the two groups （F（1,1） = 4.587, P = 0.048）, and one-way ANOVA showed no significant difference in swimming speed between the two groups （F（1,1） = 1.528, P = 0.237）. （4） In the visual cue test, all rats reached the platform within 15 seconds, with no significant difference （F（1,1） = 0.579, P = 0.459）. （5） During experimentation, all rats increased in body mass, but there was no difference between the two groups （F（1,1） = 0.05, P = 0.943）. At day 28 of 0.05% lead exposure, the blood lead level was 29.72 μg/L in the lead exposure group and 5.86 μg/L in the control group （P 〈 0.01）. CONCLUSION： The present results revealed low-level lead exposure significantly impaired spatial reference memory and spatial working memory, but had no effect on spatial learning.
基金National Natural Science Foundation Project of China(No.31560294)Guangxi Degree and Postgraduate Education Reform Project in 2021(No.JGY2021208)。
文摘Objective:To investigate the possible mechanism of microRNA-9-5p(miR-9-5p)and Ras homologous gene family A(RHOA)in aluminum-induced cognitive dysfunction in rats.Methods:According to the principle of randomization,48 Wistar rats were randomly divided into four groups(n=12)of blank control,low dose,medium dose and high dose.The blank control group was gavaged daily saline,and the other three dose groups were given daily gavage AlCl3 aqueous solution at three doses of 25 mg/kg,50 mg/kg,and 100 mg/kg to create a rat model of cognitive impairment for three months.The water maze(MWM)positioning navigation experiment was used to record the time t(s),namely,the incubation period,on the platform of rats,and the incubation period of each group was used to determine whether the rats in the infected group had learning and memory impairment.Hematoxylin-eosin(HE)and Nissl stains observed the pathological changes of nerve cells in the hippocampus of the four groups.Western blot detected the protein expression levels of RHOA and cranial neurotrophic factor(BDNF)in fresh rat hippocampal tissues.RT-qPCR detected the mRNA expression of miR-9-5p,RHOA,and BDNF in rat hippocampal tissues.Results:The results of Morris water maze positioning navigation test showed that the incubation period of each group was calculated on the 1st,3rd and 5th days of the experiment,and the motor incubation period of the infected group was higher than that of the control group.The results of HE staining showed that the rat nerve cells in the control group were morphologically intact,the staining was clear,the nucleus was clearly visible,and the edge of the cell membrane was sharp.The rat neurons in the infected group were damaged to varying degrees,the nucleus gradually dissolved,the cytoplasmic staining became deeper,the edges of the cell membrane were blurred and disordered,and the cells were deformed and arranged disordered.The results of Nissl staining showed that the well-stained Nissl body particles were visible in the nerve cells of rats in the control group,and the dissipation of Nissl bodies in the nerve cells of the infected group was reduced,and the staining was shallow.The results of RT-qPCR showed that compared with the control group,the mRNA expression of miR-9-5p and BDNF was decreased in the infected group,and the mRNA expression of RHOA was increased(P<0.05 or P<0.001).The Western blot results showed that compared with the control group,the relative expression of BDNF in the three infected groups was decreased,and the relative expression of RHOA increased(P<0.05).Conclusion:In aluminum-induced cognitive impairment,miR-9-5p is downregulated and RHOA is upregulatd.
文摘Ivane S. Beritashvili’s doctrine of image-driven behavior was established in the late 1920s and finally extended in his books in English (1965;1971). It bears a strong resemblance to the concepts of purposive behavior and “cognitive maps” developed in parallel by Edward C. Tolman (1932;1948) and significantly anticipated respective modern concepts. John O’Keefe and his disciples May-Britt Moser and Edvard I. Moser received the Nobel Prize in 2014 for their discoveries of cells that constitute a navigation system in the brain. The latter fact brings us to the pioneers of the study of the spatial orientation of animals that figuratively speaking, provided the giant’s shoulders on which O’Keefe and the Mosers stood to receive their award. Beritashvili and Tolman upheld the holistic and goal-directed nature of spatial behavior. A major contribution of Beritashvili to the science of animal behavior was the demonstration of the universality of learning following a single presentation of an object vitally important to the animal: either a food object or a noxious signal. Beritashvili showed that such “image-driven” behavior has a strong spatial component, i.e., the image is projected into a definite point in space. Thus, he came to maintain that there is a class of behavior that is image-driven that does not require a repetition of associations. Tolman made several significant contributions to the field of experimental psychology. He thought of learning as developing from bits of knowledge and cognitions about the environment and how the organism relates to it. He examined the role that reinforcement plays in the way that rats learn their way through complex mazes. These experiments eventually led to the theory of latent learning which describes learning that occurs in the absence of an obvious reward. Tolman also strongly advocated the theory that rats learn the place where they have been rewarded rather than the particular movements required to get there. To a great extent, Tolman’s work determined the direction of American psychology in the 1930s-1950s. The contribution of Beritashvili and Tolman, thus, is the groundwork of modern studies of spatial cognitive processes in human and nonhuman animals.
文摘Background： The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San （DSS） is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus. Methods： A total of 36 rats were randornly divided into three groups： （ 1 ） Sham group （n = 12）, rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment： （2） experimental tooth movement （ETM） group （n - 12）, rats received saline treatment and ETM： （3） DSS ＋ ETM （DETM） group （n = 12）, rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Monis water maze test was evaluated： immunofluorescent histochemistry was used to identity astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus. Results： Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased cornpared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus （DG）. Conclusions： Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG ofhippocampus in the ETM group rats may be related with the decline of the ability of learning and rnernory. The ability to change the synaptic plasticity in hippocarnpus after DSS administration may be correlated with the alleviation of impairment of learn and memory atter ETM treatment.
基金the National Science Foundation of China (81774406 and 31571041)the Guangdong Innovative and Entrepreneurial Research Team Program (Natural Science) (2017KCXTD006)+1 种基金Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2016)the Scientific Research and Innovation Team Program of Guangzhou University of Chinese Medicine (2017KYTD03)
文摘Rho-associated kinases(ROCKs)are serinethreonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton.Two ROCK isoforms(ROCK1 and ROCK2)are expressed in the mammalian central nervous system.Although ROCK activity has been implicated in synapse formation,whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear.Here,we used a genetic approach to address this long-standing question.Both Rock1^+/- and Rock2^+/- mice had impaired glutamatergic transmission,reduced spine density,and fewer excitatory synapses in hippocampal CA1 pyramidal neurons.In addition,both Rockl^+/- and Rock2^+/- mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests.However,the spine morphology of CA1 pyramidal neurons was altered only in Rock2^+/- but not Rock1^+/- mice.In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time.Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.
