小鼠大脑中嗅受体olfr544的表达及其在阿尔茨海默氏病模型中的功能研究

嗅受体不仅在鼻腔内表达，还广泛表达在其他非嗅觉组织中，发挥重要生理作用。研究表明，嗅受体olfr544高度表达在阿尔茨海默氏病（AD）小鼠脑内，其表达量与该病的发病进程相关。我们前期研究发现，olfr544的激活剂能在体外促进神经细胞突起生长，降低氧化应激引起的ROS水平，提高神经细胞pCREB水平，提示olfr544可能在AD中起着保护神经的作用。本项目将以内源性表达olfr544的N2a细胞系及小鼠为研究对象，通过细胞模型和动物模型，拟解决：1）olfr544在AD小鼠脑内的表达及分布；2）激活状态的olfr544是否具有保护神经细胞的功能，及其在AD细胞模型中的作用和介导的信号通路；3）olfr544的过表达和敲减对小鼠认知功能及信号通路的影响。本研究拟通过阐明嗅受体olfr544在AD模型中的作用及其分子机制，为大脑中嗅受体的功能研究提供理论和实验依据。

Olfactory receptors are not only expressed in the nasal cavity, but also widely expressed in other non-olfactory tissues and play important roles. Studies have shown that the olfactory receptor olfr544 is highly expressed in the brain of Alzheimer's disease (AD) mice, and the expression level is related to the stage of the disease. Our previous studies have found that the activator of olfr544 can promote the neurite outgrowth in vitro, reduce the level of ROS caused by oxidative stress, and increase the level of pCREB in nerve cells, suggesting that olfr544 may play protective role in AD. In this project, N2a cell lines and mice which express olfr544 endogenously will be used as subjects, through cell models and animal models, intending to solve the following three questions: 1) The expression and distribution of olfr544 in the brain of AD mice; 2) Whether activated olfr544 has the function of protecting nerve cells, and how does it work in AD cell model; 3) The effect on cognitive function and signaling pathway in mice which overexpression or knocking of olfr544. This research intends to elucidate the function and molecular mechanisms of olfr544 in the brain of AD mice, so as to provide experimental basis for the studies of olfactory receptors in brain.