The neuroimmune system is required for normal neural processes, including modulation of cognition, emotion, and adaptive behaviors. Aberrant neuroimmune activation is associated with dysregulation of memory and emotion, though the precise mechanisms at play are complex and highly context dependent. Sex differences in neuroimmune activation and function further complicate our understanding of its roles in cognitive and affective regulation. Here, we characterized the physiological sickness and inflammatory response of the hippocampus following intracerebroventricular (ICV) administration of a synthetic viral mimic, polyinosinic:polycytidylic acid (poly I:C), in both male and female C57Bl/6N mice. We observed that poly I:C induced weight loss, fever, and elevations of cytokine and chemokines in the hippocampus of both sexes. Specifically, we found transient increases in gene expression and protein levels of IL-1α, IL-1β, IL-4, IL-6, TNFα, CCL2, and CXCL10, where males showed a greater magnitude of response compared with females. Only males showed increased IFNα and IFNγ in response to poly I:C, whereas both males and females exhibited elevations of IFNβ, demonstrating a specific sex difference in the anti-viral response in the hippocampus. Our data suggest that type I interferons are one potential node mediating sex-specific cytokine responses and neuroimmune effects on cognition. Together, these findings highlight the importance of using both males and females and analyzing a broad set of inflammatory markers in order to identify the precise, sex-specific roles for neuroimmune dysregulation in neurological diseases and disorders.

中文翻译：

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对多聚 I:C 中枢给药的神经免疫反应的性别差异和相似性

正常的神经过程需要神经免疫系统，包括认知、情绪和适应性行为的调节。异常的神经免疫激活与记忆和情绪的失调有关，尽管起作用的精确机制是复杂的并且高度依赖于上下文。神经免疫激活和功能的性别差异使我们对其在认知和情感调节中的作用的理解进一步复杂化。在这里，我们描述了雄性和雌性 C57Bl/6N 小鼠在脑室 (ICV) 内注射合成病毒模拟物聚肌苷：聚胞苷酸 (poly I:C) 后海马的生理疾病和炎症反应。我们观察到聚 I:C 会导致两性海马体中的体重减轻、发烧和细胞因子和趋化因子升高。具体来说，我们发现 IL-1α、IL-1β、IL-4、IL-6、TNFα、CCL2 和 CXCL10 的基因表达和蛋白质水平瞬时增加，与女性相比，男性表现出更大的反应幅度。只有男性对 poly I:C 的反应显示出增加的 IFNα 和 IFNγ，而男性和女性都表现出 IFNβ 的升高，这表明海马体中的抗病毒反应存在特定的性别差异。我们的数据表明，I 型干扰素是一种潜在的节点，可介导性别特异性细胞因子反应和神经免疫对认知的影响。总之，这些发现强调了使用男性和女性并分析广泛的炎症标志物的重要性，以便确定神经免疫失调在神经系统疾病和紊乱中的精确、性别特异性作用。