Sex differences in prefrontal cortex microglia morphology: impact of a two-hit model of adversity throughout development

Neuroimmune mechanisms play critical roles in brain development and can be impacted by early life adversity.  Microglia are the resident immune cells in the brain, with both sex-specific and region-specific developmental profiles.  Since early life adversity is associated with several neuropsychiatric disorders with developmental pathogeneses, here we investigated the degree to which maternal separation (MS) impacted microglia over development. Microglia are dynamic cells that alter their morphology in accordance with their activation states and in response to stressors.  While males and females reportedly display different microglial morphology in several brain regions over development and following immune and psychological challenges, little is known about such differences in the prefrontal cortex (PFC), which regulates several early life adversity-attributable disorders.  Additionally, little is known about the potential for early life adversity to prime microglia for later immune ch...

神经免疫机制在大脑发育过程中发挥关键作用，且可受到早期不良经历（early life adversity）的影响。小胶质细胞（Microglia）是大脑内的固有免疫细胞，其发育特征兼具性别特异性与脑区特异性。鉴于早期不良经历与多种具有发育性发病机制的神经精神疾病密切相关，本研究探究了母婴分离（MS）在发育进程中对小胶质细胞的影响程度。小胶质细胞属于动态细胞群体，可根据自身激活状态及对应激源的响应改变形态。尽管已有研究表明，雄性与雌性个体在发育过程中及受到免疫与心理应激后，多个脑区的小胶质细胞形态存在显著差异，但对于前额叶皮层（prefrontal cortex, PFC）中的此类差异却知之甚少——而前额叶皮层正是多种由早期不良经历引发的疾病的核心调控脑区。此外，目前对于早期不良经历是否可致敏小胶质细胞，使其在后续免疫挑战（immune ch...）中产生异常应答的相关研究仍有待进一步探索。