OBJECTIVE Lychee seed,a famous traditional Chinese medicine,recently were reported to improve the learning and memory abilities in mice.However,it is still unclear whether lychee seed saponins(LSS)can improve the cogn...OBJECTIVE Lychee seed,a famous traditional Chinese medicine,recently were reported to improve the learning and memory abilities in mice.However,it is still unclear whether lychee seed saponins(LSS)can improve the cognitive function and associated mechanisms.METHODS In present studies,we established the Alzheimer disease(AD)model by injecting Aβ25-35 into the lateral ventricle of rats.Then the spatial learning and memory abilities of LSS-treated rats were evaluated with the Morris water maze,meanwhile the protein expressions of AKT,GSK3β and Tau in the hippocampal neuron were analyzed by immunohistochemistry and Western blotting.RESULTS The results showed LSS can improve the cognitive functions of AD rats through shortening the escape latency,increasing the number across the platform,platform quadrant dwell time and the percentage of the total distance run platform quadrant.The protein expression of AKT was significantly up-regulated and that of GSK3β and Tau were decreased remarkably in the hippocampal CA1 area.CONCLUSION Our study is the first to show that LSS significantly improve the cognitive function and prevent hippocampal neuronal injury of the rats with AD by activation of the PI3K/AKT/GSK3βsignaling pathway,suggesting LSS may be developed into the nutrient supplement for the treatment of AD.展开更多
OBJECTIVE Cognitive dysfunc⁃tion is a core disturbance of schizophrenia,appear to emerge from impaired neural activity.The anterior cingulate cortex(ACC)is an integra⁃tion hub for higher-order thalamic inputs impor⁃ta...OBJECTIVE Cognitive dysfunc⁃tion is a core disturbance of schizophrenia,appear to emerge from impaired neural activity.The anterior cingulate cortex(ACC)is an integra⁃tion hub for higher-order thalamic inputs impor⁃tant for complex cognitive tasks such as learning and memory processes,attention and social interaction.Parvalbumin(PV)interneurons could filter information at pyramidal neurons of ACC,and the abnormal PV interneurons have been observed in both humans and animal models of schizophrenia.However,the mechanisms of PV interneurons in ACC regulating cognition in schizophrenia is poorly understood.METHODS The pregnant mice were injected with methyl⁃azoxymethanol acetate(MAM)on gestational day(GD)16 for the neurodevelopmental MAM model of schizophrenia in our study.We investi⁃gated the cognitive behaviors by a serious of tests such as pre-pulse inhibition,Y maze,novel object and novel location recognition and the intrinsic excitability of PV interneurons and inhibi⁃tory synaptic transmission onto pyramidal cells localized in layer 5 of ACC by whole-cell record⁃ings.Further,the PV interneurons were regulat⁃ed by designer receptor exclusively activated by a designer drug(DREADD)system and the D-serine,a co-agonist of N-methyl-D-aspartate(NMDA)receptors.RESULTS①MAM mice showed the cognitive deficits and hypo-excitability of PV interneurons in ACC.②Restoration of PV interneuron activity in ACC improved cognitive function in MAM mice.③Inhibition of PV interneu⁃ron activity in ACC was sufficient to cause cogni⁃tive dysfunction in control mice.④NMDA recep⁃tors of PV interneurons in ACC were impaired in MAM mice.⑤Deficits of NMDA receptor sig⁃naling specifically in PV interneurons and of cog⁃nitive behaviors in MAM mice were rescued by D-serine.CONCLUSION PV interneurons in ACC are closely related to cognitive function in the MAM model of schizophrenia and D-serine maybe a potential therapy for schizophrenia.展开更多
基金supported by Science and Technology Planning Project of Sichuan Province(2008SZ0050,14JC0798)Educational Commission of Sichuan Province(10ZA035,15ZA0155)+1 种基金Science and Technology Program of Luzhou(2015-S-43,2016LZXNYD-T03)Key Development Program of Southwest Medical University(2010ZD-010)
文摘OBJECTIVE Lychee seed,a famous traditional Chinese medicine,recently were reported to improve the learning and memory abilities in mice.However,it is still unclear whether lychee seed saponins(LSS)can improve the cognitive function and associated mechanisms.METHODS In present studies,we established the Alzheimer disease(AD)model by injecting Aβ25-35 into the lateral ventricle of rats.Then the spatial learning and memory abilities of LSS-treated rats were evaluated with the Morris water maze,meanwhile the protein expressions of AKT,GSK3β and Tau in the hippocampal neuron were analyzed by immunohistochemistry and Western blotting.RESULTS The results showed LSS can improve the cognitive functions of AD rats through shortening the escape latency,increasing the number across the platform,platform quadrant dwell time and the percentage of the total distance run platform quadrant.The protein expression of AKT was significantly up-regulated and that of GSK3β and Tau were decreased remarkably in the hippocampal CA1 area.CONCLUSION Our study is the first to show that LSS significantly improve the cognitive function and prevent hippocampal neuronal injury of the rats with AD by activation of the PI3K/AKT/GSK3βsignaling pathway,suggesting LSS may be developed into the nutrient supplement for the treatment of AD.
文摘OBJECTIVE Cognitive dysfunc⁃tion is a core disturbance of schizophrenia,appear to emerge from impaired neural activity.The anterior cingulate cortex(ACC)is an integra⁃tion hub for higher-order thalamic inputs impor⁃tant for complex cognitive tasks such as learning and memory processes,attention and social interaction.Parvalbumin(PV)interneurons could filter information at pyramidal neurons of ACC,and the abnormal PV interneurons have been observed in both humans and animal models of schizophrenia.However,the mechanisms of PV interneurons in ACC regulating cognition in schizophrenia is poorly understood.METHODS The pregnant mice were injected with methyl⁃azoxymethanol acetate(MAM)on gestational day(GD)16 for the neurodevelopmental MAM model of schizophrenia in our study.We investi⁃gated the cognitive behaviors by a serious of tests such as pre-pulse inhibition,Y maze,novel object and novel location recognition and the intrinsic excitability of PV interneurons and inhibi⁃tory synaptic transmission onto pyramidal cells localized in layer 5 of ACC by whole-cell record⁃ings.Further,the PV interneurons were regulat⁃ed by designer receptor exclusively activated by a designer drug(DREADD)system and the D-serine,a co-agonist of N-methyl-D-aspartate(NMDA)receptors.RESULTS①MAM mice showed the cognitive deficits and hypo-excitability of PV interneurons in ACC.②Restoration of PV interneuron activity in ACC improved cognitive function in MAM mice.③Inhibition of PV interneu⁃ron activity in ACC was sufficient to cause cogni⁃tive dysfunction in control mice.④NMDA recep⁃tors of PV interneurons in ACC were impaired in MAM mice.⑤Deficits of NMDA receptor sig⁃naling specifically in PV interneurons and of cog⁃nitive behaviors in MAM mice were rescued by D-serine.CONCLUSION PV interneurons in ACC are closely related to cognitive function in the MAM model of schizophrenia and D-serine maybe a potential therapy for schizophrenia.
