Zhou Hao, Wang Jiesi, Zhang Yu, Shao Feng, Wang Weiwen
Beijing Key Laboratory of Behavior and Mental Health, School of Psychological and Cognitive Sciences, Peking University, Beijing, China.
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Front Integr Neurosci. 2020 Sep 4;14:551676. doi: 10.3389/fnint.2020.551676. eCollection 2020.
According to the microglial hypothesis of schizophrenia, the hyperactivation of microglia and the release of proinflammatory cytokines lead to neuronal loss, which is highly related to the onset of schizophrenia. Recent studies have demonstrated that fractalkine (CX3CL1) and its receptor CX3CR1 modulate the function of microglia. Thus, the present study aimed to determine whether microglial CX3CR1 plays a role in schizophrenia-related behaviors. A classical animal model of schizophrenia, social isolation (from postnatal days 21-56), was used to induce schizophrenia-related behaviors in C57BL/6J and CX3CR1 mice, and the expression of the microglial CX3CR1 protein was examined in several brain areas of the C57BL/6J mice by Western blot analysis. The results revealed that social isolation caused deficits in the prepulse inhibition (PPI) in the C57BL/6J mice but not in the CX3CR1 mice and increased locomotor activity in both the C57BL/6J mice and the CX3CR1 mice. Moreover, the CX3CR1 protein level was increased in the medial prefrontal cortex, nucleus accumbens, and hippocampus of the isolated C57BL/6J mice. These findings suggested that the function of microglia regulated by CX3CR1 might participate in schizophrenia-related behaviors.
根据精神分裂症的小胶质细胞假说，小胶质细胞的过度激活和促炎细胞因子的释放会导致神经元丢失，这与精神分裂症的发病高度相关。最近的研究表明，趋化因子（CX3CL1）及其受体CX3CR1调节小胶质细胞的功能。因此，本研究旨在确定小胶质细胞CX3CR1是否在精神分裂症相关行为中起作用。采用一种经典的精神分裂症动物模型，即社会隔离（出生后第21天至56天），在C57BL/6J和CX3CR1小鼠中诱导精神分裂症相关行为，并通过蛋白质免疫印迹分析检测C57BL/6J小鼠几个脑区中小胶质细胞CX3CR1蛋白的表达。结果显示，社会隔离导致C57BL/6J小鼠的前脉冲抑制（PPI）出现缺陷，但在CX3CR1小鼠中未出现，并且使C57BL/6J小鼠和CX3CR1小鼠的运动活性均增加。此外，在隔离的C57BL/6J小鼠的内侧前额叶皮质、伏隔核和海马体中，CX3CR1蛋白水平升高。这些发现表明，由CX3CR1调节的小胶质细胞功能可能参与精神分裂症相关行为。
