Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.
Nat Commun. 2023 May 11;14(1):2721. doi: 10.1038/s41467-023-38373-0.
While the precise processes underlying a sex bias in the development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to the disease pathogenesis. When we mimicked an early systemic viral infection or applied murine cytomegalovirus (MCMV) systemically in neonatal female and male mice, only male adolescent mice presented behavioral deficits, including reduced social behavior and cognition. This was paralleled by an increased amount of infiltrating T cells in the brain parenchyma, enhanced interferon-γ (IFNγ) signaling, and epigenetic reprogramming of microglial cells. These microglial cells showed increased phagocytic activity, which resulted in abnormal loss of excitatory synapses within the hippocampal brain region. None of these alterations were seen in female adolescent mice. Our findings underscore the early postnatal period's susceptibility to cause sex-dependent long-term CNS deficiencies following infections.
虽然中枢神经系统（CNS）疾病性别偏向发展的具体过程尚不清楚，但越来越多的证据表明，早期的免疫激活可能会导致疾病的发病机制。当我们模拟早期的全身病毒感染或在新生雌性和雄性小鼠中全身应用鼠巨细胞病毒（MCMV）时，只有雄性青春期小鼠表现出行为缺陷，包括社交行为和认知能力下降。这与脑实质中浸润的 T 细胞数量增加、干扰素-γ（IFNγ）信号增强以及小胶质细胞的表观遗传重编程相平行。这些小胶质细胞表现出增强的吞噬活性，导致海马脑区兴奋性突触的异常丢失。在雌性青春期小鼠中没有观察到这些变化。我们的研究结果强调了新生儿期易受感染后引起性别依赖性的长期 CNS 缺陷。
