In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodeling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodeling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events. From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

在大脑中，星形胶质细胞通过各种释放的因子和膜结合蛋白调节突触和血管室的形状和功能。因此，星形胶质细胞活动失衡会对大脑发育产生严重的负面影响，导致严重病理的发生。临床和临床前研究表明，神经发育（ND）和神经精神（NP）疾病中不同受影响大脑区域的星形胶质细胞数量、形态、分子组成和星形胶质细胞依赖性过程发生变化。星形胶质细胞在出生后早期大脑发育的关键时期增殖、分化和成熟，这是神经胶质细胞依赖性调节突触形成/消除之间适当平衡的升高的时间窗口，这对于完善突触连接至关重要。因此，在关键时期改变这些过程的任何内在和/或外在因素都可能导致异常的突触重塑和精神障碍的发作。星形胶质细胞在突触和血管区室之间的特殊桥接位置进一步使它们能够“计算”大脑状态，从而在血液中分泌因子，这些因子可以作为不同健康或疾病状况的诊断生物标志物。在这里，我们收集了关于出生后早期大脑发育关键时期星形发生和星形胶质细胞介导的神经元网络重塑调节的最新进展，重点是突触消除。然后，我们提出了替代假设，认为这些过程中的异常参与了 ND 和 NP 疾病的发生。鉴于众所周知的男性和女性之间某些大脑疾病的患病率存在​​差异，我们还讨论了对这些神经发育事件的假定的性别依赖性影响。从转化的角度来看，了解年龄和性别依赖性星形胶质细胞特异性分子和功能变化可能有助于识别健康和疾病中不同细胞（功能障碍）功能的生物标志物，有利于诊断工具的开发或针对特定疾病选择量身定制的治疗方案。男性/女性患者。