Tay Tuan Leng, Béchade Catherine, D'Andrea Ivana, St-Pierre Marie-Kim, Henry Mathilde S, Roumier Anne, Tremblay Marie-Eve
Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.
Front Mol Neurosci. 2018 Jan 4;10:421. doi: 10.3389/fnmol.2017.00421. eCollection 2017.
Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia-specific markers, and the availability of compounds that target these cells selectively , we consider the prospect of disease intervention via the microglial route.
小胶质细胞是中枢神经系统（CNS）中主要的免疫反应细胞和专职吞噬细胞，已被证明对大脑发育和内环境稳定至关重要。这些细胞在整个生命周期的各个阶段呈现出广泛的表型，尤其是在中枢神经系统疾病中。它们在所有神经病理学中的普遍存在使得重新审视它们在稳态和疾病状态下的不同作用变得十分必要。该领域的一个主要问题是确定小胶质细胞的聚集和表型转化是发病机制的主要原因，还是对疾病发作的潜在神经保护反应。最近，我们对小胶质细胞的起源和内环境稳定的理解有了爆发式增长，揭示了它们在塑造神经回路和突触可塑性方面的作用，这使我们能够在认知控制和精神疾病的背景下讨论它们的新功能。与其他神经胶质细胞相比，小胶质细胞独特的中胚层起源和基因特征也使它们成为治疗药物开发的一个有趣靶点。在这里，我们综述了小胶质细胞的生理作用、它们对环境风险因素（如母体感染、早期生活压力、饮食不均衡）影响的贡献，以及它们对发育过程中引发的精神疾病（如纳苏-哈科拉病（NHD）、遗传性弥漫性白质脑病伴球形细胞、雷特综合征、自闭症谱系障碍（ASD）和强迫症（OCD））或成年期引发的精神疾病（如酒精和药物滥用、重度抑郁症（MDD）、双相情感障碍（BD）、精神分裂症、饮食失调和睡眠障碍）的影响。此外，我们讨论了认知衰老背景下小胶质细胞功能的变化，并综述了它们在老年成人神经退行性疾病（如阿尔茨海默病和帕金森病）中的意义。考虑到最近对小胶质细胞特异性标志物的鉴定，以及选择性靶向这些细胞的化合物的可用性，我们考虑了通过小胶质细胞途径进行疾病干预的前景。
