Peripheral viral infection can substantially alter brain function. We have previously shown that intraperitoneal (i.p.) injection of a viral mimetic, polyinosinic-polycytidylic acid (PIC), engenders hyperexcitability of cerebral neurons. Because neuronal activity is invariably associated with their expression of the Cfos gene, the present study was undertaken to determine whether PIC challenge also increases neuronal c-fos protein level. Female C57BL/6 mice were i.p. injected with PIC, and neuronal c-fos was analyzed in the motor cortex by immunohistochemistry. PIC challenge instigated a robust increase in the number of c-fos-positive neurons. This increase reached approximately tenfold over control at 24 h. Also, the c-fos staining intensity of individual neurons increased. AMG-487, a specific inhibitor of the chemokine receptor CXCR3, profoundly attenuated the accumulation of neuronal c-fos, indicating the activation of CXCL10/CXCR3 axis as the trigger of the process. Together, these results show that the accumulation of c-fos is a viable readout to assess the response of cerebral neurons to peripheral PIC challenge, and to elucidate the underlying molecular mechanisms.

外周病毒感染可以显着改变大脑功能。我们之前已经表明，腹膜内 (ip) 注射病毒模拟物聚肌苷聚胞苷酸 (PIC) 会导致脑神经元过度兴奋。因为神经元活动总是与它们的Cfos表达有关基因，本研究旨在确定 PIC 攻击是否也会增加神经元 c-fos 蛋白水平。雌性 C57BL/6 小鼠腹腔注射 PIC，并通过免疫组织化学分析运动皮层中的神经元 c-fos。PIC 挑战促使 c-fos 阳性神经元的数量大幅增加。这种增加在 24 小时达到了大约 10 倍于对照。此外，单个神经元的 c-fos 染色强度增加。趋化因子受体 CXCR3 的特异性抑制剂 AMG-487 显着减弱了神经元 c-fos 的积累，表明 CXCL10/CXCR3 轴的激活是该过程的触发因素。总之，这些结果表明，c-fos 的积累是评估脑神经元对外周 PIC 挑战的反应的可行读数，