阿尔茨海默病（AD）病理过程中神经元兴奋性和突触功能发生改变，具体机制有待进一步阐明。研究表明Neuregulin1（NRG1）及其受体ErbB4参与神经元兴奋性和突触可塑性调节并影响AD病理进程，也有报道TREK通道参与神经元兴奋性调节并对学习记忆功能产生影响。我们新发现AD病理过程中ErbB4、TREK通道蛋白显著下调，并且NRG1可缓解Aβ诱导的海马神经元死亡，上调TREK通道蛋白表达并通过其受体激活TREK通道，提示AD中NRG1-ErbB4可能参与调控TREK通道，从而调节神经元兴奋性和发挥神经保护作用。本项目拟在瞬时表达系统和原代培养神经元上明确NRG1-ErbB4对TREK通道的作用特点，进而采用AD细胞、动物模型和AD患者脑组织，阐明NRG1-ErbB4是否通过调控TREK通道影响神经元兴奋性和AD病理进程并探索其机制，为进一步揭示AD的发病机制和防治药物研究提供研究基础。

The mechanisms underlying the neuronal excitability and synaptic function changes in Alzheimer's disease (AD) pathology remain largely unclear. Studies have shown that neuregulin 1 (NRG1) and its receptor ErbB4 may be involved in the pathological process of AD, as well as in regulating neuronal excitability and synaptic plasticity. Studies have also shown that the TREK channels are involved in the regulation of neuronal excitability and exert impact on learning and memory functions. Our previous results have shown that, ErbB4 and TREK channel proteins were significantly down-regulated in the pathological process of AD, in addition, NRG1 could significantly alleviate the hippocampal neuronal death induced by β-amyloid (Aβ), and up-regulate the protein expression and function of TREK channels through activating ErbB4 receptors. These results suggest that NRG1-ErbB4 signaling may be involved in the regulation of TREK channels, thereby regulating neuronal excitability and playing a neuroprotective role in the pathological process of AD. We will first identify the characteristics of the roles of NRG1-ErbB4 signaling in TREK channels regulation in transient expression systems and primary cultured neurons. Besides, we will further clarify whether NRG1-ErbB4 signaling could modulate the neuronal excitability and the AD neuropathology through the regulation of TREK channels by using AD cellular and animal models and AD patient brain tissues. Above researches may provide us with useful references and an experimental basis for further AD pathogenesis clarification, AD prevention and remedy development.