title: Transient Receptor Potential-canonical 1 is Essential for Environmental Enrichment-Induced Cognitive Enhancement and Neurogenesis.
abstract: 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.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lai-Ling
authors.initials: LL
authors.lastname: Du
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 8, Longyuan Road, Nanshan District, Shenzhen, China.
authors.forename: Xi-Fei
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Department of Pediatrics Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Da-Min
authors.initials: DM
authors.lastname: Chai
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Bing-Jin
authors.initials: BJ
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. wangjz@mail.hust.edu.cn.|Co-innovation Center of Neuroregeneration, Nantong, China. wangjz@mail.hust.edu.cn.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zhouxinwen@hust.edu.cn.
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D004777:Environment; D004924:Escape Reaction / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006799:Housing, Animal; D008297:Male; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D011897:Random Allocation; D050052:TRPC Cation Channels / Q000096:biosynthesis* / Q000172:deficiency*
chemical_list: D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1
keywords: Environmental enrichment;neurogenesis; Hippocampus; Spatial memory; Transient receptor potential-canonical 1