BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxi...BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxide synthase （nNOS）-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING： The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005. MATERIALS： Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 uL kainic acid （0.4 mg/mL） into the hippocampus. METHODS： The mice were randomized into three groups （n = 16）： model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5uL physiological saline into the hippocampus, and 2 days later, they received an intragastfic administration of physiological saline. Each mouse received two intragastric administrations （1 mL solution once） per day, for a total of 35 days. MAIN OUTCOME MEASURES： Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device. RESULTS： At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups （P 〉 0.05）. Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group （P 〈 0.05）. However, the control group was not different from the chlorogenic acid-treated group （P 〉 0.05）. At day 7 following intervention, the number of correct responses in the Y-maze test was greater in the chlorogenic acid-treated group than in the model group. CONCLUSION： Chlorogenic acid protects kainic acid-induced injury to nNOS-positive neurons in the hippocampal CA1-4 regions, thereby ameliorating learning and memory impairment.展开更多
Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D...Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.展开更多
Defatted hickory meal(DHM),a by-product of hickory oil production,is a protein source rich in essential amino acids.In this study,the functional properties of DHM hydrolysate(DHMH)were assessed using in vitro and in v...Defatted hickory meal(DHM),a by-product of hickory oil production,is a protein source rich in essential amino acids.In this study,the functional properties of DHM hydrolysate(DHMH)were assessed using in vitro and in vivo assays in context to its antioxidant and memory-enhancing effects.To induce memory impairment,D-galactose(D-gal)was administered to mice at a dose of 120 mg/kg body weight per day,and DHMH was orally administered at doses of 300,600,and 1000 mg/kg body weight per day for 8 weeks.DHMH treatment led to improved memory performance in D-ga-induced memory-impaired mice,as observed in the Morris water maze test.Furthermore,DHMH mitigated the accumulation of amyloidβ_(1-42)triggered by D-gal exposure.Notably,high-dose DHMH significantly reduced the elevation of pro-inflammatory markers,including tumor necrosis factor alpha,interleukin 1β,and interleukin 6.Additionally,DHMH prevented the decline in total superoxide dismutase activity,glutathione peroxidase activity,and glutathione levels,while reducing malondialdehyde content in D-gal-induced mice,indicative of its antioxidant properties.Moreover,DHMH treatment effectively prevented histological alterations in neurons within the hippocampal CA1 area induced by D-gal.Collectively,our findings suggest that DHMH may counteract memory dysfunctions resulting from oxidative stress injury in the brain positioning it as a potential candidate for use as a functional food.展开更多
Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiabl...Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiable matter(USM),a composition of highly active ingredients found in walnut oil,has demonstrated antioxidant effects.This study aims to explore the neuroprotective effects of USM on d-galactose-treated C57BL/6 mice and elucidate its underlying mechanism,which was validated in PC12 cells treated with d-galactose.The results of behavioral tests demonstrated that USM significantly improved cognitive deficits associated with aging.The morphological analysis demonstrated that USM effectively alleviated hippocampal neuronal damage,synaptic impairment,and mitochondrial dysfunction induced by d-galactose.Furthermore,USM significantly increases the antioxidant enzymes activity while reducing the malondialdehyde and reactive oxygen species levels.The results suggest that USM can mitigate age-related symptoms caused by d-galactose by activating the nuclear factor erythroid-2-related factor 2 signaling pathway,which enhances the expression of antioxidant enzymes,restore redox balance,and improves synaptic and mitochondrial functions.This has a positive on improving cognition and memory disorders in elderly mice.展开更多
In study,we investigated the effect of treatment with combination of walnut peptides with molecular weight<3 kDa and ginsenoside Rg1(<3 kDa+Rg1)on scopolamine-induced cognitive impairment in mice and the mechani...In study,we investigated the effect of treatment with combination of walnut peptides with molecular weight<3 kDa and ginsenoside Rg1(<3 kDa+Rg1)on scopolamine-induced cognitive impairment in mice and the mechanism of brain-derived neurotrophic factor(BDNF)/tyrosine kinase B(TrKB)/cAMP response element-binding protein(CREB)signaling pathway in PC12 cells.In behavioral experiments,<3 kDa+Rg1 treatment improved the memorizing ability of mice.Treatment with<3 kDa+Rg1 significantly regulated the function of neurotransmitters and effectively improved the morphology of the neurons determined by hematoxylin and eosin(H&E),Nissl,and Golgi staining.Additionally,immunohistochemistry showed that the<3 kDa+Rg1 treatment significantly decreased acetylcholinesterase(AChE)activity and increased choline acetyl transferase(ChAT)content in the hippocampus.The treatment upregulated vesicular acetylcholine transporter(VAChT),activated the BDNF/TrKB/CREB signaling pathway,improved the remodeling of dendritic spines,and enhanced cholinergic functions.In the scopolamine-induced PC12 cells,combination treatment increased thioredoxin-1(Trx-1)expression after administering TrKB and activated signaling pathway.The results showed combination of<3 kDa+Rg1 activated the BDNF/TrKB/CREB signaling pathway by regulating function of neurotransmitters and enhanced cholinergic function to decrease cognitive impairment.展开更多
Background:Therapy in the latent period is favorable for retarding the process of epileptogenesis.Recently,we have discovered that the activated sigma-1 receptor(Sig-1R)attenuates the hippocampus pathological injury a...Background:Therapy in the latent period is favorable for retarding the process of epileptogenesis.Recently,we have discovered that the activated sigma-1 receptor(Sig-1R)attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis.But the molecular mechanism needs further investigation.Methods:PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice.After the treatment of PRE-084,the pro-inflammatory cytokines,neuropathological traits,and the level of mitochondrial translocator assembly and maintenance 41 homolog(TAMM41)in the hippocampus were examined.The mode in which the Sig-1R interacts with TAMM41 was explored.The role of TAMM41 in the protecting effect of PRE-084 was established.Results:PRE-084 inhibited the growth of pro-inflammatory cytokines,reduced the formation of gliosis,alleviated neuronal damage in the hippocampus,and attenu-ated memory impairment in the latent period of epileptogenesis.The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice.The Sig-1R bound with TAMM41 directly,maintaining the stability of TAMM41.Knockdown of TAMM41 reversed the protective effect of PRE-084,and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084.Conclusion:We presented the concept of the“sigma-1 receptor–TAMM41 axis”and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.展开更多
The content of total flavonoids in an extract of Ginkgo biloba, called GBE50, is 44% by weight. This is significantly greater than that in a standard extract of Ginkgo biloba, designated EGB761. To date, the mechanism...The content of total flavonoids in an extract of Ginkgo biloba, called GBE50, is 44% by weight. This is significantly greater than that in a standard extract of Ginkgo biloba, designated EGB761. To date, the mechanisms by which GBE50 and EGB761 function remain poorly understood. In the present study, an experimental rat model of aging was induced by intraperitoneal injection of D-galactose, followed by intragastric perfusion of GBE50 （30, 60 mg/kg）, or EGB761 （60 mg/kg）. The water maze scores and hippocampal CA1 synaptic plasticity were evaluated. In the place navigation test, the GBE50 group rats did better than EGB761, while similar scores were obtained in the spatial probe test, and in the platform-switched test. In addition, long-term potentiation was significantly enhanced following high-frequency stimulation in the GBE50 and EGB761 groups, compared with the model group. These results demonstrate that GBE50 and EGB761 improved the learning and memory of aging rats. In particular, GBE50 administered at the 60 mg/kg dose exhibited superior effects over EGB761 at the same 60 mg/kg dose. Furthermore, the enhancement of hippocampal synaptic plasticity may be an underlying mechanism.展开更多
BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects o...BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in comparison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a scopolamine-induced mouse model of dementia. DESIGN： Randomized controlled animal study. SETTINGS： Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical College （purity of 79.6% by using a phenol-concentrated sulphate acid method）, and hydrogen bromine acid scopolamine injection solution （SCO） by Shanghai Hefeng Pharmaceutical Co., Ltd. METHODS： This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform （latent period） for 30 minutes, they were determined to have learned the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme （GSH-Px）, superoxide dismutase （SOD）, and the content of malondialdehyde （MDA） were assayed using an UV spectrophotometer. （2） The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded. MAIN OUTCOME MEASURE： （1） Numbers of error responses within 5 minutes on the platform. （2） GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. （3） Numbers and duration of mouth-opening breaths of the isolated mouse head. RESULTS： Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. （1） Effects of PSP on learning in mice： The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions （P 〈 0.05）. （2） Effects of PSP on memory in mice： The number of errors in the step-down test in the model group was higher than in the normal control group （P 〈 0.01）. Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups （P 〈 0.01）. （3） Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue： SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group （P 〉 0.05）. （4） Effects of PSP on acute cerebral ischemia in mice： The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head （P 〈 0.05, 0.01）. CONCLUSION： PSP can improve learning and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.展开更多
Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, lead...Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.展开更多
Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats e...Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than controls.Microglia positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM rats.Long Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM rats.Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the MWM.Most importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM rats.Overall,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.展开更多
Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and ...Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and clinical treatment strategies for this problem are lacking.Metformin,used as a first-line treatment for type 2 diabetes mellitus,is reported to reduce the effects of chemobrain.Recently,several studies have examined the effect of metformin in rescuing chemobrain.This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.展开更多
Objective: To investigate whether the extract from the nacreous layer of pearl oysters(nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods: Nacre extract was prepared ...Objective: To investigate whether the extract from the nacreous layer of pearl oysters(nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods: Nacre extract was prepared from the inner shell layer of pearl oyster. Effects of nacre extract on scopolamine-induced memory impairment were estimated using novel object recognition test, Y-maze test, and Barnes maze test Effect of nacre extract on mRNA expressions which are genes associated with memory in the hippocampus was investigated using semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) analysis.Results: Administration of nacre extract led to the protection against scopolamine-induced impairments in object recognition, short-term memory, and spatial memory. Treatment with nacre extract reversed the mRNA expression of brain-derived neurotrophic factor(BDNF) and Homer protein homolog 1(Homer-1 a) in the hippocampus, which decreased with the treatment of scopolamine. Conclusions: These results suggest that nacre extract has attenuating effects on memory impairments induced by scopolamine through the increase in mRNA expression of BDNF and Homer-1 a.展开更多
Aim: To observe the rats’ learning and memory acquisition ability disturbance induced by BI-D1870. Methods: Male SD rats were randomly divided into control group, solvent control group and BI-D1870 group. The rats in...Aim: To observe the rats’ learning and memory acquisition ability disturbance induced by BI-D1870. Methods: Male SD rats were randomly divided into control group, solvent control group and BI-D1870 group. The rats in the control group were intraperitoneally injected with saline, while those in the solvent control group were intraperitoneally injected with DMSO + sulfobutyl-β-cyclodextrin solvent, and those in the BI-D1870 group were intraperitoneally injected with BI-D1870. All the rats’ appearance and behavior were daily observed, and body weight was recorded on the day 15, 30, 45, 60, 75 and 82 of BI-D1870 injected. Morris water maze was used to screen the rats’ learning and memory acquisition ability on the day 22 - 25, 52 - 55, and 82 - 85 of training by BI-D1870 treated. The successful rates of the rats’ memory impairment were respectively calculated for three times screening. Results: During the whole experiment, there was no obvious difference in appearance and fur color in all rats. The rats’ agitation began to appear on the day 10th of BI-D1870 given. The agitation rats’ number and rats’ body weight gradually increased along with BI-D1870 treated (P P Conclusion: Intraperitoneal injection of BI-D1870 can induce the rats’ learning and memory acquisition ability disorder.展开更多
Prior to development of diffusion tensor imaging （DTI）, there were many difficulties in visualization and estimation of the Papez circuit in the live human brain （Papez, 1995）. Diffusion tensor tractography （DTT...Prior to development of diffusion tensor imaging （DTI）, there were many difficulties in visualization and estimation of the Papez circuit in the live human brain （Papez, 1995）. Diffusion tensor tractography （DTT）, derived from DTI, allows for identification and visualization of neural tracts in the Papez circuit （Concha et al., 2005; Kwon et al., 2010; Granziera et al., 2011; Jang and Yeo, 2013; Jang et al., 2014a）. In the current study, using DTT, we report on a patient who showed injured thalamocortical tract between the anterior thalamic nuclei and the cingulate gyrus following a putaminal hemorrhage.展开更多
Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the mem...Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HILFN.Methods Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^(-/-)) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.Results The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilamentpositive nerve fibers in the cornu ammonis 1(CA1) and dentate gyrus(DG) hippocampal areas in wildtype mice. However, TRPV4^(-/-)mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.Conclusion TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus,which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.展开更多
OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS...OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.展开更多
With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstr...With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.展开更多
The fornix, a part of the Papez circuit, transfers information of episodic memory between the medial temporal lobe and the medial diencephalon （Aggleton and Brown, 1999）. The right medial temporal lobe is known to b...The fornix, a part of the Papez circuit, transfers information of episodic memory between the medial temporal lobe and the medial diencephalon （Aggleton and Brown, 1999）. The right medial temporal lobe is known to be specialized for visual memory and the left medial temporal lobe for verbal memory （Tucker et al., 1988; Aegleton and Brown, 1999）.展开更多
To evaluate the effect of acute high-altitude exposure on sensory and short-term memory using interactive software,we transported 30 volunteers in a sport utility vehicle to a 4280 m plateau within3 h.We measured thei...To evaluate the effect of acute high-altitude exposure on sensory and short-term memory using interactive software,we transported 30 volunteers in a sport utility vehicle to a 4280 m plateau within3 h.We measured their memory performance on the plain（initial arrival）and 3 h after arrival on the plateau using six measures.展开更多
Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum a...Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum americanum aqueous extract in mice pilocarpine model of epilepsy and associated memory loss. Mice were administered orally Chrysanthellum americanum aqueous extract (27.69, 69.22, 138.45, 276.9 mg/kg, prepared from the whole part) for test groups, intraperitoneally 300 mg/kg sodium valproate for the positive control group or orally 10 mL/kg distilled water for the negative control group, respectively, during a period of seven consecutive days. On the first day, temporal lobe epilepsy was induced by intraperitoneal injection of 360 mg/kg pilocarpine one hour after the administration of different treatment to mice, and the occurrence of status epilepticus was evaluated. On the second day, the anticonvulsant property was measured after the intraperitoneal injection of a sub-convulsive dose of picrotoxin (1 mg/kg). On the seventh day, the anti-amnesic properties of the extract were evaluated in the epileptic mice using the T-maze and open field paradigms. The results show that Chrysanthellum americanum extract significantly (p Chrysanthellum americanum (276.9 mg/kg) likewise sodium valproate (300 mg/kg) significantly (p Chrysanthellum americanum aqueous extract has anticonvulsant effects against pilocarpine induced-epileptic seizures and memory impairment. These properties could be mediated by the amelioration of antioxidant defense system and cholinergic neurotransmission in epileptic mice, which could partly justify the use of Chrysanthellum americanum in the traditional medicine for the treatment of epilepsy.展开更多
文摘BACKGROUND： Clinical practice and modern pharmacology have confirmed that chlorogenic acid can ameliorate learning and memory impairments. OBJECTIVE： To observe the effects of chlorogenic acid on neuronal nitric oxide synthase （nNOS）-positive neurons in the mouse hippocampus, and to investigate the mechanisms underlying the beneficial effects of chlorogenic acid on learning and memory. DESIGN, TIME AND SETTING： The present randomized, controlled, neural cell morphological observation was performed at the Institute of Neurobiology, Central South University between January and May 2005. MATERIALS： Forty-eight female, healthy, adult, Kunming mice were included in this study. Learning and memory impairment was induced with an injection of 0.5 uL kainic acid （0.4 mg/mL） into the hippocampus. METHODS： The mice were randomized into three groups （n = 16）： model, control, and chlorogenic acid-treated. At 2 days following learning and memory impairment induction, intragastric administration of physiological saline or chlorogenic acid was performed in the model and chlorogenic acid-treated groups, respectively. The control mice were administered 0.5uL physiological saline into the hippocampus, and 2 days later, they received an intragastfic administration of physiological saline. Each mouse received two intragastric administrations （1 mL solution once） per day, for a total of 35 days. MAIN OUTCOME MEASURES： Detection of changes in hippocampal and cerebral cortical nNOS neurons by immunohistochemistry; determination of spatial learning and memory utilizing the Y-maze device. RESULTS： At day 7 and 35 after intervention, there was no significant difference in the number of nNOS-positive neurons in the cerebral cortex between the model, chlorogenic acid, and control groups （P 〉 0.05）. Compared with the control group, the number of nNOS-positive neurons in the hippocampal CA1-4 region was significantly less in the model group （P 〈 0.05）. However, the control group was not different from the chlorogenic acid-treated group （P 〉 0.05）. At day 7 following intervention, the number of correct responses in the Y-maze test was greater in the chlorogenic acid-treated group than in the model group. CONCLUSION： Chlorogenic acid protects kainic acid-induced injury to nNOS-positive neurons in the hippocampal CA1-4 regions, thereby ameliorating learning and memory impairment.
文摘Background:Over the past few decades,a threefold increase in obesity and type 2 diabetes(T2D)has placed a heavy burden on the health-care system and society.Previous studies have shown correlations between obesity,T2D,and neurodegenera-tive diseases,including dementia.It is imperative to further understand the relation-ship between obesity,T2D,and cognitive deficits.Methods:This investigation tested and evaluated the cognitive impact of obesity and T2D induced by high-fat diet(HFD)and the effect of the host genetic background on the severity of cognitive decline caused by obesity and T2D in collaborative cross(CC)mice.The CC mice are a genetically diverse panel derived from eight inbred strains.Results:Our findings demonstrated significant variations in the recorded phenotypes across different CC lines compared to the reference mouse line,C57BL/6J.CC037 line exhibited a substantial increase in body weight on HFD,whereas line CC005 ex-hibited differing responses based on sex.Glucose tolerance tests revealed significant variations,with some lines like CC005 showing a marked increase in area under the curve(AUC)values on HFD.Organ weights,including brain,spleen,liver,and kidney,varied significantly among the lines and sexes in response to HFD.Behavioral tests using the Morris water maze indicated that cognitive performance was differentially affected by diet and genetic background.Conclusions:Our study establishes a foundation for future quantitative trait loci map-ping using CC lines and identifying genes underlying the comorbidity of Alzheimer's disease(AD),caused by obesity and T2D.The genetic components may offer new tools for early prediction and prevention.
基金supported by the Key Research and Development Project of Hanzhou(20231203A03)。
文摘Defatted hickory meal(DHM),a by-product of hickory oil production,is a protein source rich in essential amino acids.In this study,the functional properties of DHM hydrolysate(DHMH)were assessed using in vitro and in vivo assays in context to its antioxidant and memory-enhancing effects.To induce memory impairment,D-galactose(D-gal)was administered to mice at a dose of 120 mg/kg body weight per day,and DHMH was orally administered at doses of 300,600,and 1000 mg/kg body weight per day for 8 weeks.DHMH treatment led to improved memory performance in D-ga-induced memory-impaired mice,as observed in the Morris water maze test.Furthermore,DHMH mitigated the accumulation of amyloidβ_(1-42)triggered by D-gal exposure.Notably,high-dose DHMH significantly reduced the elevation of pro-inflammatory markers,including tumor necrosis factor alpha,interleukin 1β,and interleukin 6.Additionally,DHMH prevented the decline in total superoxide dismutase activity,glutathione peroxidase activity,and glutathione levels,while reducing malondialdehyde content in D-gal-induced mice,indicative of its antioxidant properties.Moreover,DHMH treatment effectively prevented histological alterations in neurons within the hippocampal CA1 area induced by D-gal.Collectively,our findings suggest that DHMH may counteract memory dysfunctions resulting from oxidative stress injury in the brain positioning it as a potential candidate for use as a functional food.
基金supported by the National Key Research and Development Program(2022YFD1600402)Hebei Provincial Major Science and Technology Achievement Transformation Project(21287101Z)Hebei Provincial Innovation and Entrepreneurship Team Project(215A7102D)。
文摘Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations.Dietary interventions are being considered as potential strategies for delaying age-related dysfunction.Unsaponifiable matter(USM),a composition of highly active ingredients found in walnut oil,has demonstrated antioxidant effects.This study aims to explore the neuroprotective effects of USM on d-galactose-treated C57BL/6 mice and elucidate its underlying mechanism,which was validated in PC12 cells treated with d-galactose.The results of behavioral tests demonstrated that USM significantly improved cognitive deficits associated with aging.The morphological analysis demonstrated that USM effectively alleviated hippocampal neuronal damage,synaptic impairment,and mitochondrial dysfunction induced by d-galactose.Furthermore,USM significantly increases the antioxidant enzymes activity while reducing the malondialdehyde and reactive oxygen species levels.The results suggest that USM can mitigate age-related symptoms caused by d-galactose by activating the nuclear factor erythroid-2-related factor 2 signaling pathway,which enhances the expression of antioxidant enzymes,restore redox balance,and improves synaptic and mitochondrial functions.This has a positive on improving cognition and memory disorders in elderly mice.
基金funded by the Research and Product Development of Key Technologies for Efficient Utilization of Walnut Meal(20210203125SF)Changchun 2021 Local Transformation of Scientific and Technological Achievements Guide Special(21KY05).
文摘In study,we investigated the effect of treatment with combination of walnut peptides with molecular weight<3 kDa and ginsenoside Rg1(<3 kDa+Rg1)on scopolamine-induced cognitive impairment in mice and the mechanism of brain-derived neurotrophic factor(BDNF)/tyrosine kinase B(TrKB)/cAMP response element-binding protein(CREB)signaling pathway in PC12 cells.In behavioral experiments,<3 kDa+Rg1 treatment improved the memorizing ability of mice.Treatment with<3 kDa+Rg1 significantly regulated the function of neurotransmitters and effectively improved the morphology of the neurons determined by hematoxylin and eosin(H&E),Nissl,and Golgi staining.Additionally,immunohistochemistry showed that the<3 kDa+Rg1 treatment significantly decreased acetylcholinesterase(AChE)activity and increased choline acetyl transferase(ChAT)content in the hippocampus.The treatment upregulated vesicular acetylcholine transporter(VAChT),activated the BDNF/TrKB/CREB signaling pathway,improved the remodeling of dendritic spines,and enhanced cholinergic functions.In the scopolamine-induced PC12 cells,combination treatment increased thioredoxin-1(Trx-1)expression after administering TrKB and activated signaling pathway.The results showed combination of<3 kDa+Rg1 activated the BDNF/TrKB/CREB signaling pathway by regulating function of neurotransmitters and enhanced cholinergic function to decrease cognitive impairment.
基金This project was supported by grants from the National Natural Science Foundation of China(Grant Nos.81872847 and 82173803)the Science and Technology Planning Project of Xuzhou(Grant No.KC22256)the Science and Technology Developing Fund of The Affiliated Hospital of Xuzhou Medical University(Grant No.2021ZA14)。
文摘Background:Therapy in the latent period is favorable for retarding the process of epileptogenesis.Recently,we have discovered that the activated sigma-1 receptor(Sig-1R)attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis.But the molecular mechanism needs further investigation.Methods:PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice.After the treatment of PRE-084,the pro-inflammatory cytokines,neuropathological traits,and the level of mitochondrial translocator assembly and maintenance 41 homolog(TAMM41)in the hippocampus were examined.The mode in which the Sig-1R interacts with TAMM41 was explored.The role of TAMM41 in the protecting effect of PRE-084 was established.Results:PRE-084 inhibited the growth of pro-inflammatory cytokines,reduced the formation of gliosis,alleviated neuronal damage in the hippocampus,and attenu-ated memory impairment in the latent period of epileptogenesis.The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice.The Sig-1R bound with TAMM41 directly,maintaining the stability of TAMM41.Knockdown of TAMM41 reversed the protective effect of PRE-084,and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084.Conclusion:We presented the concept of the“sigma-1 receptor–TAMM41 axis”and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.
基金the Scientific Research Program of the Shanghai Science and Technology Commission,No.09ZR1432100the Key Subject Construction Program of Shanghai Education Commission,No.J50301the Scientific Research Innovation Program of Shanghai Education Commission,No.08YZ59
文摘The content of total flavonoids in an extract of Ginkgo biloba, called GBE50, is 44% by weight. This is significantly greater than that in a standard extract of Ginkgo biloba, designated EGB761. To date, the mechanisms by which GBE50 and EGB761 function remain poorly understood. In the present study, an experimental rat model of aging was induced by intraperitoneal injection of D-galactose, followed by intragastric perfusion of GBE50 （30, 60 mg/kg）, or EGB761 （60 mg/kg）. The water maze scores and hippocampal CA1 synaptic plasticity were evaluated. In the place navigation test, the GBE50 group rats did better than EGB761, while similar scores were obtained in the spatial probe test, and in the platform-switched test. In addition, long-term potentiation was significantly enhanced following high-frequency stimulation in the GBE50 and EGB761 groups, compared with the model group. These results demonstrate that GBE50 and EGB761 improved the learning and memory of aging rats. In particular, GBE50 administered at the 60 mg/kg dose exhibited superior effects over EGB761 at the same 60 mg/kg dose. Furthermore, the enhancement of hippocampal synaptic plasticity may be an underlying mechanism.
文摘BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in comparison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a scopolamine-induced mouse model of dementia. DESIGN： Randomized controlled animal study. SETTINGS： Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical College （purity of 79.6% by using a phenol-concentrated sulphate acid method）, and hydrogen bromine acid scopolamine injection solution （SCO） by Shanghai Hefeng Pharmaceutical Co., Ltd. METHODS： This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform （latent period） for 30 minutes, they were determined to have learned the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme （GSH-Px）, superoxide dismutase （SOD）, and the content of malondialdehyde （MDA） were assayed using an UV spectrophotometer. （2） The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded. MAIN OUTCOME MEASURE： （1） Numbers of error responses within 5 minutes on the platform. （2） GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. （3） Numbers and duration of mouth-opening breaths of the isolated mouse head. RESULTS： Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. （1） Effects of PSP on learning in mice： The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions （P 〈 0.05）. （2） Effects of PSP on memory in mice： The number of errors in the step-down test in the model group was higher than in the normal control group （P 〈 0.01）. Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups （P 〈 0.01）. （3） Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue： SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group （P 〉 0.05）. （4） Effects of PSP on acute cerebral ischemia in mice： The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head （P 〈 0.05, 0.01）. CONCLUSION： PSP can improve learning and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.
基金supported by National Natural Science Foundation of China [No. 81773405 to Y.Q. and No. 82173644to X.Y.]Shanxi Natural Science Foundation of China [No.202203021211246 and No. 202103021224242]。
文摘Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
基金supported by grants from the National Natural Science Foundation of China (31730040,81801115, and 81920108016)the China Postdoctoral Science Foundation (2018M642304)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China。
文摘Purinergic receptors have been reported to be involved in brain disorders.In this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than controls.Microglia positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM rats.Long Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM rats.Minocycline significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the MWM.Most importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM rats.Overall,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.
基金This work was supported by the Deanship of Scientific Research,Qassim University。
文摘Cognitive impairment caused by chemotherapy,referred to as“chemobrain,”is observed in approximately 70% of cancer survivors.However,it is not completely understood how chemotherapy induces cognitive dysfunction,and clinical treatment strategies for this problem are lacking.Metformin,used as a first-line treatment for type 2 diabetes mellitus,is reported to reduce the effects of chemobrain.Recently,several studies have examined the effect of metformin in rescuing chemobrain.This review discusses recent clinical/preclinical studies that addressed some mechanisms of chemobrain and evaluates the effect of metformin in rescuing chemobrain and its potential mechanisms of action.
文摘Objective: To investigate whether the extract from the nacreous layer of pearl oysters(nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods: Nacre extract was prepared from the inner shell layer of pearl oyster. Effects of nacre extract on scopolamine-induced memory impairment were estimated using novel object recognition test, Y-maze test, and Barnes maze test Effect of nacre extract on mRNA expressions which are genes associated with memory in the hippocampus was investigated using semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) analysis.Results: Administration of nacre extract led to the protection against scopolamine-induced impairments in object recognition, short-term memory, and spatial memory. Treatment with nacre extract reversed the mRNA expression of brain-derived neurotrophic factor(BDNF) and Homer protein homolog 1(Homer-1 a) in the hippocampus, which decreased with the treatment of scopolamine. Conclusions: These results suggest that nacre extract has attenuating effects on memory impairments induced by scopolamine through the increase in mRNA expression of BDNF and Homer-1 a.
文摘Aim: To observe the rats’ learning and memory acquisition ability disturbance induced by BI-D1870. Methods: Male SD rats were randomly divided into control group, solvent control group and BI-D1870 group. The rats in the control group were intraperitoneally injected with saline, while those in the solvent control group were intraperitoneally injected with DMSO + sulfobutyl-β-cyclodextrin solvent, and those in the BI-D1870 group were intraperitoneally injected with BI-D1870. All the rats’ appearance and behavior were daily observed, and body weight was recorded on the day 15, 30, 45, 60, 75 and 82 of BI-D1870 injected. Morris water maze was used to screen the rats’ learning and memory acquisition ability on the day 22 - 25, 52 - 55, and 82 - 85 of training by BI-D1870 treated. The successful rates of the rats’ memory impairment were respectively calculated for three times screening. Results: During the whole experiment, there was no obvious difference in appearance and fur color in all rats. The rats’ agitation began to appear on the day 10th of BI-D1870 given. The agitation rats’ number and rats’ body weight gradually increased along with BI-D1870 treated (P P Conclusion: Intraperitoneal injection of BI-D1870 can induce the rats’ learning and memory acquisition ability disorder.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology,No.2012R1A1A4A01001873
文摘Prior to development of diffusion tensor imaging （DTI）, there were many difficulties in visualization and estimation of the Papez circuit in the live human brain （Papez, 1995）. Diffusion tensor tractography （DTT）, derived from DTI, allows for identification and visualization of neural tracts in the Papez circuit （Concha et al., 2005; Kwon et al., 2010; Granziera et al., 2011; Jang and Yeo, 2013; Jang et al., 2014a）. In the current study, using DTT, we report on a patient who showed injured thalamocortical tract between the anterior thalamic nuclei and the cingulate gyrus following a putaminal hemorrhage.
基金funded by the Chongqing Postdoctoral Innovative Talent Support Program[Grant No.CQBX2021008]the Chongqing Talents Project[CQYC202105043]。
文摘Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HILFN.Methods Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^(-/-)) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.Results The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilamentpositive nerve fibers in the cornu ammonis 1(CA1) and dentate gyrus(DG) hippocampal areas in wildtype mice. However, TRPV4^(-/-)mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.Conclusion TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus,which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
文摘OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.
文摘With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.
基金supported by Basic Science Research Pro-gram through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology,No.2012R1A1A4A01001873
文摘The fornix, a part of the Papez circuit, transfers information of episodic memory between the medial temporal lobe and the medial diencephalon （Aggleton and Brown, 1999）. The right medial temporal lobe is known to be specialized for visual memory and the left medial temporal lobe for verbal memory （Tucker et al., 1988; Aegleton and Brown, 1999）.
基金supported by a grant from the National Science Foundation of China(No.81301134,81371444)a research program from the logistics department of PLA(No.CLZ15C005)
文摘To evaluate the effect of acute high-altitude exposure on sensory and short-term memory using interactive software,we transported 30 volunteers in a sport utility vehicle to a 4280 m plateau within3 h.We measured their memory performance on the plain（initial arrival）and 3 h after arrival on the plateau using six measures.
文摘Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum americanum aqueous extract in mice pilocarpine model of epilepsy and associated memory loss. Mice were administered orally Chrysanthellum americanum aqueous extract (27.69, 69.22, 138.45, 276.9 mg/kg, prepared from the whole part) for test groups, intraperitoneally 300 mg/kg sodium valproate for the positive control group or orally 10 mL/kg distilled water for the negative control group, respectively, during a period of seven consecutive days. On the first day, temporal lobe epilepsy was induced by intraperitoneal injection of 360 mg/kg pilocarpine one hour after the administration of different treatment to mice, and the occurrence of status epilepticus was evaluated. On the second day, the anticonvulsant property was measured after the intraperitoneal injection of a sub-convulsive dose of picrotoxin (1 mg/kg). On the seventh day, the anti-amnesic properties of the extract were evaluated in the epileptic mice using the T-maze and open field paradigms. The results show that Chrysanthellum americanum extract significantly (p Chrysanthellum americanum (276.9 mg/kg) likewise sodium valproate (300 mg/kg) significantly (p Chrysanthellum americanum aqueous extract has anticonvulsant effects against pilocarpine induced-epileptic seizures and memory impairment. These properties could be mediated by the amelioration of antioxidant defense system and cholinergic neurotransmission in epileptic mice, which could partly justify the use of Chrysanthellum americanum in the traditional medicine for the treatment of epilepsy.
