Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice
Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice
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Nhe5 缺陷通过上调 Bdnf/TrkB 信号增强小鼠的学习和记忆
DOI：
10.1002/ajmg.b.32600
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发表时间：
2017-12-01
影响因子：
2.8
通讯作者：
Wang, Zhugang
中科院分区：
文献类型：
--
作者：
Chen, Xuejiao;Wang, Xiyi;Wang, Zhugang
Nhe5是一种Na+/H+交换剂，主要在脑组织中表达，并被认为是树突棘生长的负调节因子。到目前为止，其在体内的生理功能尚不清楚。研究结果表明，nhe5缺陷小鼠在Morris水迷宫、新物体识别和被动回避任务中的学习记忆能力显著增强。同时，在缺乏Nhe5的海马区，突触前和突触后组分、突触体素（Syn）和突触后密度95 （PSD95）表达水平升高，提示Nhe5（-/-）小鼠神经元突触结构和功能可能发生改变。进一步研究发现，Nhe5缺乏导致Bdnf表达水平升高，随后磷酸化的TrkB和PLC水平升高，表明Bdnf/TrkB信号通路因Nhe5缺乏而被激活。此外，Nhe5（-/-）小鼠相应的脑区显示ERK/CaMKII/CREB磷酸化水平升高。综上所述，这些发现揭示了Nhe5在调节学习和记忆方面的一种新的生理功能，进一步表明Nhe5可能是改善认知的潜在治疗靶点。
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 PLC 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.