GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory

Abstract Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infu...

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Autores principales:	Enjie Liu, Ao-Ji Xie, Qiuzhi Zhou, Mengzhu Li, Shujuan Zhang, Shihong Li, Weijin Wang, Xiaochuan Wang, Qun Wang, Jian-Zhi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3fe13f4e15544536a9a098ca75068d3e
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spelling	oai:doaj.org-article:3fe13f4e15544536a9a098ca75068d3e2021-12-02T16:08:00ZGSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory10.1038/s41598-017-06173-42045-2322https://doaj.org/article/3fe13f4e15544536a9a098ca75068d3e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06173-4https://doaj.org/toc/2045-2322Abstract Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3βlox/lox mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms. We found that mice with GSK-3β deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior. Further studies demonstrated that GSK-3β deletion in DG subset inhibited hippocampal synaptic transmission and reduced levels of GluN1, GluN2A and GluN2B (NMDAR subunits), GluA1 (AMPAR subunit), PSD93 and drebrin (postsynaptic structural proteins), and synaptophysin (presynaptic protein). GSK-3β deletion also suppressed the activity-dependent neural activation and calcium/calmodulin-dependent protein kinase II (CaMKII)/CaMKIV-cAMP response element binding protein (CREB) signaling. Our data suggest that GSK-3β in hippocampal DG excitatory neurons is essential for maintaining synaptic plasticity and memory.Enjie LiuAo-Ji XieQiuzhi ZhouMengzhu LiShujuan ZhangShihong LiWeijin WangXiaochuan WangQun WangJian-Zhi WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Enjie Liu Ao-Ji Xie Qiuzhi Zhou Mengzhu Li Shujuan Zhang Shihong Li Weijin Wang Xiaochuan Wang Qun Wang Jian-Zhi Wang GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
description	Abstract Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3βlox/lox mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms. We found that mice with GSK-3β deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior. Further studies demonstrated that GSK-3β deletion in DG subset inhibited hippocampal synaptic transmission and reduced levels of GluN1, GluN2A and GluN2B (NMDAR subunits), GluA1 (AMPAR subunit), PSD93 and drebrin (postsynaptic structural proteins), and synaptophysin (presynaptic protein). GSK-3β deletion also suppressed the activity-dependent neural activation and calcium/calmodulin-dependent protein kinase II (CaMKII)/CaMKIV-cAMP response element binding protein (CREB) signaling. Our data suggest that GSK-3β in hippocampal DG excitatory neurons is essential for maintaining synaptic plasticity and memory.
format	article
author	Enjie Liu Ao-Ji Xie Qiuzhi Zhou Mengzhu Li Shujuan Zhang Shihong Li Weijin Wang Xiaochuan Wang Qun Wang Jian-Zhi Wang
author_facet	Enjie Liu Ao-Ji Xie Qiuzhi Zhou Mengzhu Li Shujuan Zhang Shihong Li Weijin Wang Xiaochuan Wang Qun Wang Jian-Zhi Wang
author_sort	Enjie Liu
title	GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
title_short	GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
title_full	GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
title_fullStr	GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
title_full_unstemmed	GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
title_sort	gsk-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3fe13f4e15544536a9a098ca75068d3e
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GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory

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