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Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice
Author(s) -
Chen Xuejiao,
Wang Xiyi,
Tang Lingyun,
Wang Jinjin,
Shen Chunling,
Liu Jianbing,
Lu Shunyuan,
Zhang Hongxin,
Kuang Ying,
Fei Jian,
Wang Zhugang
Publication year - 2017
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32600
Subject(s) - tropomyosin receptor kinase b , synaptophysin , morris water navigation task , neuroscience , dendritic spine , creb , hippocampus , phosphorylation , long term potentiation , synaptic plasticity , water maze , hippocampal formation , mapk/erk pathway , chemistry , psychology , microbiology and biotechnology , biology , neurotrophic factors , medicine , receptor , transcription factor , immunohistochemistry , biochemistry , gene
Nhe5, a Na + /H + exchanger, is predominantly expressed in brain tissue and is proposed to act as a negative regulator of dendritic spine growth. Up to now, its physiological function in vivo remains unclear. Here we show that Nhe5‐deficient mice exhibit markedly enhanced learning and memory in Morris water maze, novel object recognition, and passive avoidance task. Meanwhile, the pre‐ and post‐synaptic components, synaptophysin (Syn) and post‐synaptic density 95 (PSD95) expression levels were found increased in hippocampal regions lacking of Nhe5, suggesting a possible alterations in neuronal synaptic structure and function in Nhe5 −/− mice. Further study reveals that Nhe5 deficiency leads to higher Bdnf expression levels, followed by increased phosphorylated TrkB and PLCγ levels, indicating that Bdnf/TrkB signaling is activated due to Nhe5 deficiency. Moreover, the corresponding brain regions of Nhe5 −/− mice display elevated ERK/CaMKII/CREB phosphorylation levels. Taken together, these findings uncover a novel physiological function of Nhe5 in regulating learning and memory, further implying Nhe5 as a potential therapeutic target for improving cognition.