Artificial intelligence is currently achieving impressive success in all fields.However,autonomous navigation remains a major challenge for AI.Reinforcement learning is used for target navigation to simulate the inter...Artificial intelligence is currently achieving impressive success in all fields.However,autonomous navigation remains a major challenge for AI.Reinforcement learning is used for target navigation to simulate the interaction between the brain and the environment at the behavioral level,but the Artificial Neural Network trained by reinforcement learning cannot match the autonomous mobility of humans and animals.The hippocampus–striatum circuits are considered as key circuits for target navigation planning and decision-making.This paper aims to construct a bionic navigation model of reinforcement learning corresponding to the nervous system to improve the autonomous navigation performance of the robot.The ventral striatum is considered to be the behavioral evaluation region,and the hippocampal–striatum circuit constitutes the position–reward association.In this paper,a set of episode cognition and reinforcement learning system simulating the mechanism of hippocampus and ventral striatum is constructed,which is used to provide target guidance for the robot to perform autonomous tasks.Compared with traditional methods,this system reflects the high efficiency of learning and better Environmental Adaptability.Our research is an exploration of the intersection and fusion of artificial intelligence and neuroscience,which is conducive to the development of artificial intelligence and the understanding of the nervous system.展开更多
Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function....Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.展开更多
The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to t...The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.展开更多
Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the...Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.展开更多
Neurological disorders like Alzheimer’s disease have a significant impact on the lives and health of the elderly as the aging population con-tinues to grow.Doctors can achieve effective prevention and treatment of Al...Neurological disorders like Alzheimer’s disease have a significant impact on the lives and health of the elderly as the aging population con-tinues to grow.Doctors can achieve effective prevention and treatment of Alzheimer’s disease according to the morphological volume of hippocam-pus.General segmentation techniques frequently fail to produce satisfactory results due to hippocampus’s small size,complex structure,and fuzzy edges.We develop a new SC-Net model using complete brain MRI images to achieve high-precision segmentation of hippocampal structures.The proposed network improves the accuracy of hippocampal structural segmentation by retaining the original location information of the hippocampus.Extensive experimental results demonstrate that the proposed SC-Net model is signif-icantly better than other models,and reaches a Dice similarity coefficient of 0.885 on Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset.展开更多
The use of ocean bottom seismometers provides an effective means of studying the process and the dynamic of cold seeps by continuously recording micro-events produced by sub-seafloor fluid migration.We deployed a four...The use of ocean bottom seismometers provides an effective means of studying the process and the dynamic of cold seeps by continuously recording micro-events produced by sub-seafloor fluid migration.We deployed a four-component Ocean Bottom Seismometer(OBS)at an active site of the Haima cold seep from 6 November to 19 November in 2021.Here,we present the results of this short-term OBS monitoring.We first examine the OBS record manually to distinguish(by their distinctive seismographic signatures)four types of events:shipping noises,vibrations from our remotely operated vehicle(ROV)operations,local earthquakes,and short duration events(SDEs).Only the SDEs are further discussed in this work.Such SDEs are similar to those observed in other sea areas and are interpreted to be correlated with sub-seafloor fluid migration.In the OBS data collected during the 14-day monitoring period.We identify five SDEs.Compared to the SDE occurrence rate observed in other cold seep regions,five events is rather low,from which it could be inferred that fluid migration,and subsequent gas seepage,is not very active at the Haima site.This conclusion agrees with multi-beam and chemical observations at that site.Our observations thus provide further constraint on the seepage activity in this location.This is the first time that cold seep-related SDEs have been identified in the South China Sea,expanding the list of sea areas where SDEs are now linked to cold seep fluid migration.展开更多
Bivalve shell fossils,cemented by authigenic carbonates,are widely spread in the Haima cold seep,Qiongdongnan Basin of the South China Sea(SCS).In this study,we examined an element profile of Gigantidas platifrons in ...Bivalve shell fossils,cemented by authigenic carbonates,are widely spread in the Haima cold seep,Qiongdongnan Basin of the South China Sea(SCS).In this study,we examined an element profile of Gigantidas platifrons in the Haima cold seeps at a water depth of 1381 m.Based on the scanning electron microscope(SEM)analyses,the prismatic layer and nacreous layer were identified,which are characterized by prismatic structure and stratified structure,respectively.In addition,the profile can be subdivided into two parts:altered and unaltered zones.Laser inductively coupled plasma mass spectrometry(LA-ICP-MS)mapping shows that the element concentrations of the altered zones were influenced by the authigenic carbonate rocks,whereas the element concentrations of unaltered zones remain stable.In-situ X-ray diffraction(XRD)analyses show that the mineral constituent of the prismatic layer is mainly composed of aragonite.Along with the growth profile,Mg/Ca ratios of unaltered zones have minor variations,ranging 0.72-0.97 mmol/mol(mean=0.87 mmol/mol),with estimated temperatures of 3.8-4.1℃,indicating that the temperature of the surrounding seawater remains constant and agree with the measured data of 3.9℃which was conducted by a conductivity-temperature-depth system(CTD).The minor variations of Ba/Ca ratios(0.01-0.06 mmol/mol;mean=0.04 mmol/mol)indicate a relatively stabilized salinity of the surrounding seawater.S/Ca ratios show large variations of 0.04-4.15 mmol/mol(mean=1.37 mmol/mol).S/Ca ratios have regular variations which generally correspond to the variations of the Mg/Ca ratios,highlighting that the S/Ca ratios of bivalve shells show the potential to reflect the growth rate of the Gigantides.However,further studies should be carried out on the understanding of the links between the S/Ca ratios and seepage intensity of cold-seep fluids.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
基金funded by National Key R&D Program of China to Fusheng Zha with Grant numbers 2020YFB13134Natural Science Foundation of China to Fusheng Zha with Grant numbers U2013602,52075115,51521003,61911530250.
文摘Artificial intelligence is currently achieving impressive success in all fields.However,autonomous navigation remains a major challenge for AI.Reinforcement learning is used for target navigation to simulate the interaction between the brain and the environment at the behavioral level,but the Artificial Neural Network trained by reinforcement learning cannot match the autonomous mobility of humans and animals.The hippocampus–striatum circuits are considered as key circuits for target navigation planning and decision-making.This paper aims to construct a bionic navigation model of reinforcement learning corresponding to the nervous system to improve the autonomous navigation performance of the robot.The ventral striatum is considered to be the behavioral evaluation region,and the hippocampal–striatum circuit constitutes the position–reward association.In this paper,a set of episode cognition and reinforcement learning system simulating the mechanism of hippocampus and ventral striatum is constructed,which is used to provide target guidance for the robot to perform autonomous tasks.Compared with traditional methods,this system reflects the high efficiency of learning and better Environmental Adaptability.Our research is an exploration of the intersection and fusion of artificial intelligence and neuroscience,which is conducive to the development of artificial intelligence and the understanding of the nervous system.
基金supported by grant PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by"ERDF A way of making Europe"(to RL)supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/21/180501/000064)+3 种基金Universidad de Castilla-La Mancha (2023-GRIN-34187)(to RL).Grant PID201 9-104921RB-I00/MCI/AEI/10.13039/501100011033 (to AGO)the Foundation for Applied Medical Research,the University of Navarra (Pamplona,Spain)for financial supporthe Asociación de Amigos of the University of Navarra for the grant (to SB)Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha (to AMB)
文摘Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resilience in Tg2576 mice.
基金funded by the National Natural Science Foundation of China,Nos.82171363(to PL),82171321(to XL),82171458(to XJ)the Youth Nova Program of Shaanxi,No.2021KJXX-19(to PL)。
文摘The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.
基金supported by the National Natural Science Foundation of China (U2004134)Zhengzhou University (140/32310295) to NWH+2 种基金by Science Foundation Ireland(19/FFP/6437 and 14/IA/2571) to MJRa scholarship granted by the China Scholarship Council (CSC20200704504 7) to YY
文摘Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.
文摘Neurological disorders like Alzheimer’s disease have a significant impact on the lives and health of the elderly as the aging population con-tinues to grow.Doctors can achieve effective prevention and treatment of Alzheimer’s disease according to the morphological volume of hippocam-pus.General segmentation techniques frequently fail to produce satisfactory results due to hippocampus’s small size,complex structure,and fuzzy edges.We develop a new SC-Net model using complete brain MRI images to achieve high-precision segmentation of hippocampal structures.The proposed network improves the accuracy of hippocampal structural segmentation by retaining the original location information of the hippocampus.Extensive experimental results demonstrate that the proposed SC-Net model is signif-icantly better than other models,and reaches a Dice similarity coefficient of 0.885 on Alzheimer’s Disease Neuroimaging Initiative(ADNI)dataset.
基金supported by the Key Research and Development Project of Guangdong Province(Grant:2020B1111510001)supported by the Project of Sanya Yazhou Bay Science and Technology City(Grant No:SCKJ-JYRC-2022-14)the National Natural Science Foundation of China(Grant No:92262304).
文摘The use of ocean bottom seismometers provides an effective means of studying the process and the dynamic of cold seeps by continuously recording micro-events produced by sub-seafloor fluid migration.We deployed a four-component Ocean Bottom Seismometer(OBS)at an active site of the Haima cold seep from 6 November to 19 November in 2021.Here,we present the results of this short-term OBS monitoring.We first examine the OBS record manually to distinguish(by their distinctive seismographic signatures)four types of events:shipping noises,vibrations from our remotely operated vehicle(ROV)operations,local earthquakes,and short duration events(SDEs).Only the SDEs are further discussed in this work.Such SDEs are similar to those observed in other sea areas and are interpreted to be correlated with sub-seafloor fluid migration.In the OBS data collected during the 14-day monitoring period.We identify five SDEs.Compared to the SDE occurrence rate observed in other cold seep regions,five events is rather low,from which it could be inferred that fluid migration,and subsequent gas seepage,is not very active at the Haima site.This conclusion agrees with multi-beam and chemical observations at that site.Our observations thus provide further constraint on the seepage activity in this location.This is the first time that cold seep-related SDEs have been identified in the South China Sea,expanding the list of sea areas where SDEs are now linked to cold seep fluid migration.
基金Supported by the Key Research and Development Project of Guangdong Province(No.2020B1111510001)the National Natural Science Foundation of China(No.U2244224)+1 种基金the PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2020GD0802)the Guangdong Special Support Team Program(No.2019BT02H594)。
文摘Bivalve shell fossils,cemented by authigenic carbonates,are widely spread in the Haima cold seep,Qiongdongnan Basin of the South China Sea(SCS).In this study,we examined an element profile of Gigantidas platifrons in the Haima cold seeps at a water depth of 1381 m.Based on the scanning electron microscope(SEM)analyses,the prismatic layer and nacreous layer were identified,which are characterized by prismatic structure and stratified structure,respectively.In addition,the profile can be subdivided into two parts:altered and unaltered zones.Laser inductively coupled plasma mass spectrometry(LA-ICP-MS)mapping shows that the element concentrations of the altered zones were influenced by the authigenic carbonate rocks,whereas the element concentrations of unaltered zones remain stable.In-situ X-ray diffraction(XRD)analyses show that the mineral constituent of the prismatic layer is mainly composed of aragonite.Along with the growth profile,Mg/Ca ratios of unaltered zones have minor variations,ranging 0.72-0.97 mmol/mol(mean=0.87 mmol/mol),with estimated temperatures of 3.8-4.1℃,indicating that the temperature of the surrounding seawater remains constant and agree with the measured data of 3.9℃which was conducted by a conductivity-temperature-depth system(CTD).The minor variations of Ba/Ca ratios(0.01-0.06 mmol/mol;mean=0.04 mmol/mol)indicate a relatively stabilized salinity of the surrounding seawater.S/Ca ratios show large variations of 0.04-4.15 mmol/mol(mean=1.37 mmol/mol).S/Ca ratios have regular variations which generally correspond to the variations of the Mg/Ca ratios,highlighting that the S/Ca ratios of bivalve shells show the potential to reflect the growth rate of the Gigantides.However,further studies should be carried out on the understanding of the links between the S/Ca ratios and seepage intensity of cold-seep fluids.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
