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
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
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
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
Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-meth...Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-methyl-D-aspartate receptor(NMDAR)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and the excitotoxicity induced by hippocampal calcium overload.Methods Thirty-two male SD rats of SPF grade were selected and randomized into a normal group(6 rats),a shamoperation group(6 rats)and an operation group(20 rats).VD model was established with the modified Pulsinelli's four-vessel occlusion(4-VO)method.Twelve rats after successfully modeled were assigned randomly into a model group and an EA group,6 rats in each one.In the EA group,EA was delivered at bilateral"Fengchi"(GB 20)and"Sishencong"(EX-HN 1),with the continuous wave,the frequency of 2 Hz and the electric current of 1 mA.Stimulation intensity was adjusted depending on the slightly trembling of rat head.EA was given once daily,30 min each time;and EA intervention was delivered for 21 days continuously.Using Morris water maze test,the learning and memory functionwas assessed.The neuronal morphology in the hippocampal CAl was observed with HE staining;the level of glutamate(GLU)in serum and hippocampal tissue,as well as the activity of calcium pump(Ca^(2+)-ATP)in the hippocampus were detected using colorimetric method.Theprotein expression ofNMDAR,calmodulindependent protein kinase II(CaMK I),phosphorylated calmodulin-dependent protein kinase I(p-CaMK II),phosphorylated cyclic phosphoradenosine effector element binding proteins(p-CREB),CREB,,and BDNF in the hippocampal CA1 was detected using immunohistochemistry.The protein expression of NMDAR,CREB,p-CREB and BDNF in the hippocampal tissue was detected using Western blot method.Results Compared to the shamoperation group,in the model group,the escape latency was prolonged and the platform crossing times of rats were reduced(P<0.01),the hippocampal neuron structure was damaged to different degrees,the structure in hippocampal CA1 was loosened,the arrangement disorganized,with clear grid-like structure;the neuronal morphology was irregular,pyknosis and even dissolution occurred,glial cells increased,blood capillarywas dilated and the inflammatory cells were infiltrated and scattered.Thelevel of GLUintheserum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK I,p-CaMK I,CREB,p-CREB and BDNFwere reduced(P<0.01,P<0.05);and the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB were dropped(P<0.05).In comparison with the model group,in the EA group,the escape latency was shortened and the platform crossing times of rats rose(P<0.01),the arrangement was improved in the hippocampal CA1,the neuronal morphology was intact,the nucleoli were relatively clear and the pyknosis or dissolution were attenuated,the numbers of glial cells reduced relatively,the dilation of blood capillary was alleviated.The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK II,p-CaMK I,CREB,p-CREB and BDNF were elevated(P<0.05,P<0.01);the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB increased(P<0.05).Conclusion EA at"Fengchi"(GB 20)and"Sishencong"(EX-HN 1)can attenuate learning and memory impairment in VD rats,which may be obtained by reducing GLU level in hippocampal tissue,inhibiting hippocampal excitotoxicity,mediating protein expression related to the NMDAR/CREB/BDNFsignalingpathway,and maintaining neuronal survival and growth.展开更多
Objective To explore the metabolomic changes and possible mechanism of Tongdu Xingshen electroacupuncture in alleviating middle cerebral artry occlusion/reperfusion(MCAO/R) learning and memory impairment rats.Methods ...Objective To explore the metabolomic changes and possible mechanism of Tongdu Xingshen electroacupuncture in alleviating middle cerebral artry occlusion/reperfusion(MCAO/R) learning and memory impairment rats.Methods A total of 90 SD rats were divided into a control group(n=15),a sham group(n=15),and 60 MCAOR rat models were established by thread suppositing method.展开更多
The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,...The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,has lasting effects on offspring's learning and memory.Adult offspring rats of prenatal dexamethasone exposure(PDE)displayed significant impairments in novelty recognition and spatial learning memory,with some phenotypes maintained transgenerationally.PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations,and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory,but these changes failed to carry over to offspring of F5 and F7 generations.Mechanistically,altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission,which might be related to oocyte-specific high expression and transmission of miR-133a-3p.Together,PDE affects hippocampal excitatory synaptic transmission,with lasting consequences across generations,and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.展开更多
Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8...Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8 and age-matched homologous normal aging mice（SAMR1） were adopted in this study. EA stimulation at Baihui（GV 20） and Yintang（EX-HN 3） was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β（Aβ） expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results： After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion： EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.展开更多
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.
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.
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.
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Objective To explore the mechanism of electroacupuncture(EA)at"Fengchi"(GB20)and“Sishencong”(EX-HN 1)on learning and memory impairment in vascular dementia(VD)rats by observing the influences on the N-methyl-D-aspartate receptor(NMDAR)/cyclic adenosine monophosphate response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway and the excitotoxicity induced by hippocampal calcium overload.Methods Thirty-two male SD rats of SPF grade were selected and randomized into a normal group(6 rats),a shamoperation group(6 rats)and an operation group(20 rats).VD model was established with the modified Pulsinelli's four-vessel occlusion(4-VO)method.Twelve rats after successfully modeled were assigned randomly into a model group and an EA group,6 rats in each one.In the EA group,EA was delivered at bilateral"Fengchi"(GB 20)and"Sishencong"(EX-HN 1),with the continuous wave,the frequency of 2 Hz and the electric current of 1 mA.Stimulation intensity was adjusted depending on the slightly trembling of rat head.EA was given once daily,30 min each time;and EA intervention was delivered for 21 days continuously.Using Morris water maze test,the learning and memory functionwas assessed.The neuronal morphology in the hippocampal CAl was observed with HE staining;the level of glutamate(GLU)in serum and hippocampal tissue,as well as the activity of calcium pump(Ca^(2+)-ATP)in the hippocampus were detected using colorimetric method.Theprotein expression ofNMDAR,calmodulindependent protein kinase II(CaMK I),phosphorylated calmodulin-dependent protein kinase I(p-CaMK II),phosphorylated cyclic phosphoradenosine effector element binding proteins(p-CREB),CREB,,and BDNF in the hippocampal CA1 was detected using immunohistochemistry.The protein expression of NMDAR,CREB,p-CREB and BDNF in the hippocampal tissue was detected using Western blot method.Results Compared to the shamoperation group,in the model group,the escape latency was prolonged and the platform crossing times of rats were reduced(P<0.01),the hippocampal neuron structure was damaged to different degrees,the structure in hippocampal CA1 was loosened,the arrangement disorganized,with clear grid-like structure;the neuronal morphology was irregular,pyknosis and even dissolution occurred,glial cells increased,blood capillarywas dilated and the inflammatory cells were infiltrated and scattered.Thelevel of GLUintheserum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK I,p-CaMK I,CREB,p-CREB and BDNFwere reduced(P<0.01,P<0.05);and the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB were dropped(P<0.05).In comparison with the model group,in the EA group,the escape latency was shortened and the platform crossing times of rats rose(P<0.01),the arrangement was improved in the hippocampal CA1,the neuronal morphology was intact,the nucleoli were relatively clear and the pyknosis or dissolution were attenuated,the numbers of glial cells reduced relatively,the dilation of blood capillary was alleviated.The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue(P<0.01),the activity of Ca^(2+)-ATP and the protein expression of CaMK II,p-CaMK I,CREB,p-CREB and BDNF were elevated(P<0.05,P<0.01);the ratio of p-CaMK II/CaMK II and that of p-CREB/CREB increased(P<0.05).Conclusion EA at"Fengchi"(GB 20)and"Sishencong"(EX-HN 1)can attenuate learning and memory impairment in VD rats,which may be obtained by reducing GLU level in hippocampal tissue,inhibiting hippocampal excitotoxicity,mediating protein expression related to the NMDAR/CREB/BDNFsignalingpathway,and maintaining neuronal survival and growth.
文摘Objective To explore the metabolomic changes and possible mechanism of Tongdu Xingshen electroacupuncture in alleviating middle cerebral artry occlusion/reperfusion(MCAO/R) learning and memory impairment rats.Methods A total of 90 SD rats were divided into a control group(n=15),a sham group(n=15),and 60 MCAOR rat models were established by thread suppositing method.
基金supported by grants from the National Key R&D Program of China No.2020YFA0803900(Hui Wang)the National Natural Science Foundation of China No.81973405(Dan Xu),No.82122071(Dan Xu),and No.82030111(Hui Wang)。
文摘The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons.Here we explored how gestational exposure to dexamethasone,a synthetic glucocorticoid commonly used in clinical practice,has lasting effects on offspring's learning and memory.Adult offspring rats of prenatal dexamethasone exposure(PDE)displayed significant impairments in novelty recognition and spatial learning memory,with some phenotypes maintained transgenerationally.PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations,and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory,but these changes failed to carry over to offspring of F5 and F7 generations.Mechanistically,altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission,which might be related to oocyte-specific high expression and transmission of miR-133a-3p.Together,PDE affects hippocampal excitatory synaptic transmission,with lasting consequences across generations,and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.
基金Supported by the National Natureal Science Foundation of China(No.30701121)
文摘Objective： To investigate the preventive treatment effects of electroacupuncture（EA） on cognitive changes and brain damage in senescence-accelerated mouse prone 8（SAMP8） mice. Methods： The 5-month-old male SAMP8 and age-matched homologous normal aging mice（SAMR1） were adopted in this study. EA stimulation at Baihui（GV 20） and Yintang（EX-HN 3） was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β（Aβ） expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results： After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion： EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.
