Kaur Charanjit, Rathnasamy Gurugirijha, Ling Eng-Ang
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; and Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
J Neuropathol Exp Neurol. 2017 Sep 1;76(9):736-753. doi: 10.1093/jnen/nlx056.
Microglia exist in different morphological forms in the developing brain. They show a small cell body with scanty cytoplasm with many branching processes in the grey matter of the developing brain. However, in the white matter such as the corpus callosum where the unmyelinated axons are loosely organized, they appear in an amoeboid form having a round cell body endowed with copious cytoplasm rich in organelles. The amoeboid cells eventually transform into ramified microglia in the second postnatal week when the tissue becomes more compact with the onset of myelination. Microglia serve as immunocompetent macrophages that act as neuropathology sensors to detect and respond swiftly to subtle changes in the brain tissues in pathological conditions. Microglial functions are broadly considered as protective in the normal brain development as they phagocytose dead cells and sculpt neuronal connections by pruning excess axons and synapses. They also secrete a number of trophic factors such as insulin-like growth factor-1 and transforming growth factor-β among many others that are involved in neuronal and oligodendrocyte survival. On the other hand, microglial cells when activated produce a plethora of molecules such as proinflammatory cytokines, chemokines, reactive oxygen species, and nitric oxide that are implicated in the pathogenesis of many pathological conditions such as epilepsy, cerebral palsy, autism, and perinatal hypoxic-ischemic brain injury. Although many studies have investigated the origin and functions of the microglia in the developing brain, in-depth in vivo studies along with analysis of their transcriptome and epigenetic changes need to be undertaken to elucidate their full potential be it protective or neurotoxic. This would lead to a better understanding of their roles in the healthy and diseased developing brain and advancement of therapeutic strategies to target microglia-mediated neurotoxicity.
小胶质细胞在发育中的大脑中以不同的形态形式存在。在发育中大脑的灰质中，它们呈现出小的细胞体，细胞质稀少，有许多分支状突起。然而，在白质中，如胼胝体，未髓鞘化的轴突松散排列，它们呈现出阿米巴样形态，具有圆形细胞体，含有丰富的富含细胞器的细胞质。在出生后第二周，随着髓鞘形成开始组织变得更加紧密，阿米巴样细胞最终转变为分支状小胶质细胞。小胶质细胞作为具有免疫活性的巨噬细胞，充当神经病理学传感器，以检测并迅速响应病理状态下脑组织中的细微变化。在正常脑发育过程中，小胶质细胞的功能被广泛认为具有保护作用，因为它们吞噬死亡细胞，并通过修剪多余的轴突和突触来塑造神经元连接。它们还分泌许多营养因子，如胰岛素样生长因子 -1 和转化生长因子 -β 等，这些因子参与神经元和少突胶质细胞的存活。另一方面，小胶质细胞被激活时会产生大量分子，如促炎细胞因子、趋化因子、活性氧和一氧化氮，这些分子与许多病理状况的发病机制有关，如癫痫、脑瘫、自闭症和围产期缺氧缺血性脑损伤。尽管许多研究已经调查了发育中大脑中小胶质细胞的起源和功能，但仍需要进行深入的体内研究以及对其转录组和表观遗传变化的分析，以阐明它们无论是保护作用还是神经毒性的全部潜力。这将有助于更好地理解它们在健康和患病发育大脑中的作用，并推动针对小胶质细胞介导的神经毒性的治疗策略的发展。
