Excess salt intake harms brain health and cognitive functions,but whether maternal high-salt diet(HSD)affect brain development and behaviors of next generations is still unclear.Here,we reported that the offspring of ...Excess salt intake harms brain health and cognitive functions,but whether maternal high-salt diet(HSD)affect brain development and behaviors of next generations is still unclear.Here,we reported that the offspring of maternal HSD adult during pregnancy exhibit short-and long term memory deficit analyzed by the novel-place recognition assay and Barnes maze task.Moreover,using in vivo electrophysiology,we found maternal HSD also affected synaptic transmission and plasticity in hippocampus,which might underline the cognitive deficits.However,the amount of neuron had no changes in both cortex and hippocampus of adolescence and adult offspring.Finally,we identify altered expression of synaptic proteins as a potential molecular mechanism for synaptic dysfunction.展开更多
Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stre...Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood.Aim The present paper aims to predict undergraduate students1 SWB by machine learning method.Methods Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10518 Chinese adolescents.The online survey included 298 factors such as depression and personality.Quality control procedure was used to minimise biases due to online survey reports.We applied feature selection to achieve the balance between optimal prediction and result interpretation.Results The top 20 happiness risks and protective factors were finally brought into the predicting model.Approximately 90%individuals'SWB can be predicted correctly,and the sensitivity and specificity were about 92%and 90%,respectively.Conclusions This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.展开更多
Tβ4 plays an important role in the control of actin polymerization in eukaryotic cells.While its effect in multiple organs and diseases has being widely investigated,lttle is known about its influence on Alzheimer...Tβ4 plays an important role in the control of actin polymerization in eukaryotic cells.While its effect in multiple organs and diseases has being widely investigated,lttle is known about its influence on Alzheimer's disease and the possible mechanisms.Thus,we aimed to evaluate the effects and mechanisms of T94 on glial polarization and cognitive performance in APP/PS1 transgenic mice.Morris water maze test were conducted to assess memory in APP/PS1 mice.Thioflavin S staining,IHC/IF,ELISA,and immunoblotting were performed to explore Aβaccumulation,glial polarization and TLR4/NF-rB axis.We demonstrated that over expression of T94 alone alleviated Aβaccumulation of APP/PS1 mice,reversed microglia and astrocyte polarization and cognitive behavior performance.In addition,Tβ4 could downregulate both TLR4/MyD88/NF-xB p65 and p52 dependent inflammatory pathway.While combination drug of TLR4 antagonist or NF-rB p65 inhibitor exerted no further effects.展开更多
Recent animal studies showed that isoflurane exposure may lead to the disturbance of hippocampal neurogenesis and later cognitive impairment.However,much less is known about the effect of isoflurane exposure on the ne...Recent animal studies showed that isoflurane exposure may lead to the disturbance of hippocampal neurogenesis and later cognitive impairment.However,much less is known about the effect of isoflurane exposure on the neurons generated form tertiary dentate matrix of dentate gyrus,even though a great increase in granule cell population during the infantile period is principally derived from this site.To label the nascent cells from the tertiary dentate matrix of dentate gyrus,the mice were injected with bromodeoxyuridine(BrdU)on postnatal day 6(P6)and were exposed to isoflurane for 4 hat 1,8,21 day(s)and 42 day(s)after BrdU injection and the brains were collected 24 h later.The loss of different developmental stage nascent cells was assessed with BrdU,BrdU+DCX,BrdU+NeuN or BrdU+Prox-1 staining respectively.We found that the isoflurane significantly decreased the newly born(1-day old)cells and mature cells(42-day old),but not maturing cells(8-and 21-day old),suggesting isoflurane exposure exerts a neurotoxic effects on tertiary dentate matrix-originated nascent cells with an age defined pattern in mice.展开更多
Generalization is widely accepted as adaptive behavioral conditions that allow individuals to quickly respond to similar circumstances.But once overgeneralization occurs,e.g.due to the inability to suppress generalize...Generalization is widely accepted as adaptive behavioral conditions that allow individuals to quickly respond to similar circumstances.But once overgeneralization occurs,e.g.due to the inability to suppress generalized fear,it could result in anxiety,depression and related mental disorders.Endocannabinoids(eCB)are important endogenous substance,known to play a role in contextual fear memory generalization.However,less is known in terms of the precise neural mechanism and the regulation of overgeneralization,in particular,for the eCB/CB1R signaling.Using fear memory generalization task,we show that type 1 cannabinoid receptors(CB1R)in hippocampal GABAergic neurons are necessary and sufficient for avoiding overgeneralization.Suppression or deletion of CB1R in hippocampal GABAergic neurons produces overgeneralized contextual fear memory.展开更多
文摘Excess salt intake harms brain health and cognitive functions,but whether maternal high-salt diet(HSD)affect brain development and behaviors of next generations is still unclear.Here,we reported that the offspring of maternal HSD adult during pregnancy exhibit short-and long term memory deficit analyzed by the novel-place recognition assay and Barnes maze task.Moreover,using in vivo electrophysiology,we found maternal HSD also affected synaptic transmission and plasticity in hippocampus,which might underline the cognitive deficits.However,the amount of neuron had no changes in both cortex and hippocampus of adolescence and adult offspring.Finally,we identify altered expression of synaptic proteins as a potential molecular mechanism for synaptic dysfunction.
基金This work was supported by the National Key Research and Development Program(2016YFC0906400,2016YFC1307000,2016YFC0905000)the National Nature Science Foundation of China(81421061,81361120389)+2 种基金the Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)the Shanghai Leading Academic Discipline Project(B205)the Fundamental Research Funds for the Central Universities(16JXRZ01).
文摘Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood.Aim The present paper aims to predict undergraduate students1 SWB by machine learning method.Methods Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10518 Chinese adolescents.The online survey included 298 factors such as depression and personality.Quality control procedure was used to minimise biases due to online survey reports.We applied feature selection to achieve the balance between optimal prediction and result interpretation.Results The top 20 happiness risks and protective factors were finally brought into the predicting model.Approximately 90%individuals'SWB can be predicted correctly,and the sensitivity and specificity were about 92%and 90%,respectively.Conclusions This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.
文摘Tβ4 plays an important role in the control of actin polymerization in eukaryotic cells.While its effect in multiple organs and diseases has being widely investigated,lttle is known about its influence on Alzheimer's disease and the possible mechanisms.Thus,we aimed to evaluate the effects and mechanisms of T94 on glial polarization and cognitive performance in APP/PS1 transgenic mice.Morris water maze test were conducted to assess memory in APP/PS1 mice.Thioflavin S staining,IHC/IF,ELISA,and immunoblotting were performed to explore Aβaccumulation,glial polarization and TLR4/NF-rB axis.We demonstrated that over expression of T94 alone alleviated Aβaccumulation of APP/PS1 mice,reversed microglia and astrocyte polarization and cognitive behavior performance.In addition,Tβ4 could downregulate both TLR4/MyD88/NF-xB p65 and p52 dependent inflammatory pathway.While combination drug of TLR4 antagonist or NF-rB p65 inhibitor exerted no further effects.
文摘Recent animal studies showed that isoflurane exposure may lead to the disturbance of hippocampal neurogenesis and later cognitive impairment.However,much less is known about the effect of isoflurane exposure on the neurons generated form tertiary dentate matrix of dentate gyrus,even though a great increase in granule cell population during the infantile period is principally derived from this site.To label the nascent cells from the tertiary dentate matrix of dentate gyrus,the mice were injected with bromodeoxyuridine(BrdU)on postnatal day 6(P6)and were exposed to isoflurane for 4 hat 1,8,21 day(s)and 42 day(s)after BrdU injection and the brains were collected 24 h later.The loss of different developmental stage nascent cells was assessed with BrdU,BrdU+DCX,BrdU+NeuN or BrdU+Prox-1 staining respectively.We found that the isoflurane significantly decreased the newly born(1-day old)cells and mature cells(42-day old),but not maturing cells(8-and 21-day old),suggesting isoflurane exposure exerts a neurotoxic effects on tertiary dentate matrix-originated nascent cells with an age defined pattern in mice.
文摘Generalization is widely accepted as adaptive behavioral conditions that allow individuals to quickly respond to similar circumstances.But once overgeneralization occurs,e.g.due to the inability to suppress generalized fear,it could result in anxiety,depression and related mental disorders.Endocannabinoids(eCB)are important endogenous substance,known to play a role in contextual fear memory generalization.However,less is known in terms of the precise neural mechanism and the regulation of overgeneralization,in particular,for the eCB/CB1R signaling.Using fear memory generalization task,we show that type 1 cannabinoid receptors(CB1R)in hippocampal GABAergic neurons are necessary and sufficient for avoiding overgeneralization.Suppression or deletion of CB1R in hippocampal GABAergic neurons produces overgeneralized contextual fear memory.