Transient Receptor Potential-canonical 1 is Essential for Environmental Enrichment-Induced Cognitive Enhancement and Neurogenesis
Transient Receptor Potential-canonical 1 is Essential for Environmental Enrichment-Induced Cognitive Enhancement and Neurogenesis
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DOI：
10.1007/s12035-016-9758-9
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发表时间：
2017-04-01
影响因子：
5.1
通讯作者：
Zhou, Xin-Wen
中科院分区：
文献类型：
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作者：
Du, Lai-Ling;Wang, Lin;Zhou, Xin-Wen
瞬时受体电位-经典1（TRPC 1）在神经元存活、神经再生和保护神经元免受神经毒性损伤中起着至关重要的作用，但TRPC 1是否或如何影响学习和记忆尚未见报道。在这里，我们发现TRPC 1基因敲除并没有显着影响小鼠的空间学习和记忆能力时，在标准笼（SC）。有趣的是，当小鼠暴露于环境丰富（EE）4周后，TRPC 1敲除消除了EE诱导的空间记忆增强，LTP诱导和海马DG亚群的神经发生。通过立体定向将重组腺相关病毒（rAAV）-TRPC 1注入双侧海马DG亚群，我们观察到TRPC 1敲除小鼠中EE相关的神经发生、LTP诱导和认知增强被有效地挽救。EE增加了野生型小鼠中ERK、p38和环AMP反应元件结合蛋白（CREB）的磷酸化水平，而在TRPC 1敲除小鼠中未观察到ERK和CREB的活化，并且p38的磷酸化在EE-TRPC 1（-/-）和WT-EE中相同。EE增加TRPC 1表达，TRPC 1过表达增加野生型小鼠神经发生并激活ERK/CREB通路。这些结果表明TRPC 1是必不可少的EE诱导的海马神经元发生和认知增强。
Transient receptor potential-canonical 1 (TRPC1) plays a crucial role in neuronal survival, nerve regeneration, and protects neurons from neurotoxic injury, but it is not reported whether or how TRPC1 may affect learning and memory. Here, we found that TRPC1 knockout did not significantly affect the spatial learning and memory ability when the mice were housed in standard cages (SC). Interestingly, after the mice were exposed to environmental enrichment (EE) for 4 weeks, TRPC1 knockout abolished the EE-induced spatial memory enhancement, LTP induction, and neurogenesis in hippocampal DG subset. By stereotaxic infusion of the recombinant adeno-associated viruses (rAAV)-TRPC1 into the hippocampal DG subsets bilaterally, we observed that the EE-associated neurogenesis, LTP induction and the cognitive enhancement were efficiently rescued in TRPC1 knockout mice. EE increased the phosphorylation levels of ERK, p38, and cyclic AMP response element-binding protein (CREB) in wild-type mice, whereas the activation of ERK and CREB was not seen in TRPC1 knockout mice, and the phosphorylation of p38 was same in EE-TRPC1(-/-) and WT-EE. Finally, EE increased TRPC1 expression and overexpression of TRPC1 increased neurogenesis and activated ERK/CREB pathway in the wild-type mice. These findings suggest that TRPC1 is indispensable for the EE-induced hippocampal neurogenesis and cognitive enhancement.