Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice

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.

Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - October 1, 2017 Category: Genetics & Stem Cells Authors: Xuejiao Chen, Xiyi Wang, Lingyun Tang, Jinjin Wang, Chunling Shen, Jianbing Liu, Shunyuan Lu, Hongxin Zhang, Ying Kuang, Jian Fei, Zhugang Wang Tags: RESEARCH ARTICLE Source Type: research