CX3CR1信号在细颗粒污染物激活小胶质细胞影响脑认知行为及神经突触可塑性中的作用机制

Emerging evidences implicate that fine particulate matters in the polluted air can act directly or indirectly on the central nervous system, resulting in abnormal cognitive behavior, and the activation of microglia is considered to be a key factor in this process, but the specific mechanism is still unclear. Microglia has a critical role in synaptic pruning which is an important neural plasticity mechanism involved in neural balance and repair. Studies have shown that CX3CR1 signaling mediates the synaptic pruning of microglia. Therefore, we hypothesized that microglia mediates synaptic pruning in cognitive behavioral abnormalities induced by fine particulate matters via CX3CR1 signaling. In this project, in order to clarify the role and mechanism of microglia in cognitive behavioral abnormalities and synaptic plasticity disorders induced by fine particulate pollution disorders.CX3CR1 knockout mice will be used to observe the cognitive behavioral changes induced by fine particulate matters, and the changes of synaptic structure, function and the connection of neural network in the brain of olfactory bulb, prefrontal cortex, amygdala and hippocampus will be observed by means of electrophysiology, functional magnetic resonance imaging and molecular biology. We will investigate the changes of microglia function by using co-culture model of neuron and microglia and analyze their correlations. This study will reveal the mechanism of cognitive behavior abnormalities under the effect of fine particle pollutants, and provide new theoretical basises for the prevention and treatment of cognitive dysfunction caused by air pollutions.

污染空气中的细颗粒物可直接或间接作用于中枢神经系统，引起认知行为异常，而小胶质细胞激活被认为是此过程的关键因素，但具体机制不清。突触修剪是小胶质细胞参与神经组织平衡和修复的重要神经可塑性机制。研究显示CX3CR1信号介导了小胶质细胞的突触修剪作用。我们推测,小胶质细胞通过CX3CR1信号介导细颗粒物所致认知行为异常中的突触修剪作用。本项目拟应用CX3CR1基因敲除小鼠，通过细颗粒物诱导刺激，观察其认知行为学改变，通过神经电生理、功能磁共振、分子生物学等手段，从不同层面观察嗅球、前额叶、杏仁核、海马等脑区突触结构、功能及神经网络连接的改变；应用神经元和小胶质细胞共培养模型，探讨小胶质细胞功能的变化，分析其相关性，阐明小胶质细胞在细颗粒物污染所致认知行为异常及突触可塑性障碍中的作用及其机制。本研究将揭示细颗粒污染物作用下认知行为异常的发生机制，为防治空气污染所致认知功能障碍提供新的理论依据。