Microglia play a crucial role in interacting with neuronal synapses and modulating synaptic plasticity. This function is particularly significant during postnatal development, as microglia are responsible for removing excessive synapses to prevent neurodevelopmental deficits. Dysregulation of microglial synaptic function has been well-documented in various pathological conditions, notably Alzheimer's disease and multiple sclerosis. The recent application of RNA sequencing has provided a powerful and unbiased means to decipher spatial and temporal microglial heterogeneity. By identifying microglia with varying gene expression profiles, researchers have defined multiple subgroups of microglia associated with specific pathological states, including disease-associated microglia, interferon-responsive microglia, proliferating microglia, and inflamed microglia in multiple sclerosis, among others. However, the functional roles of these distinct subgroups remain inadequately characterized. This review aims to refine our current understanding of the potential roles of heterogeneous microglia in regulating synaptic plasticity and their implications for various brain disorders, drawing from recent sequencing research and functional studies. This knowledge may aid in the identification of pathogenetic biomarkers and potential factors contributing to pathogenesis, shedding new light on the discovery of novel drug targets. The field of sequencing-based data mining is evolving toward a multi-omics approach. With advances in viral tools for precise microglial regulation and the development of brain organoid models, we are poised to elucidate the functional roles of microglial subgroups detected through sequencing analysis, ultimately identifying valuable therapeutic targets.

中文翻译：

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小胶质细胞异质性在突触可塑性和大脑疾病中的作用：测序能否揭示新治疗靶点的发现？


小胶质细胞在与神经元突触相互作用和调节突触可塑性方面发挥着至关重要的作用。这一功能在出生后发育过程中尤其重要，因为小胶质细胞负责去除过多的突触以防止神经发育缺陷。小胶质细胞突触功能失调在各种病理状况下已得到充分证明，特别是阿尔茨海默病和多发性硬化症。最近 RNA 测序的应用为破译小胶质细胞的空间和时间异质性提供了一种强大且公正的手段。通过识别具有不同基因表达谱的小胶质细胞，研究人员定义了与特定病理状态相关的多个小胶质细胞亚群，包括疾病相关小胶质细胞、干扰素反应性小胶质细胞、增殖性小胶质细胞和多发性硬化症中的炎症小胶质细胞等。然而，这些不同亚组的功能作用仍未得到充分表征。本综述旨在根据最近的测序研究和功能研究，完善我们目前对异质小胶质细胞在调节突触可塑性方面的潜在作用及其对各种大脑疾病的影响的理解。这些知识可能有助于识别致病生物标志物和导致发病机制的潜在因素，为新药物靶点的发现提供新的线索。基于测序的数据挖掘领域正在朝着多组学方法发展。随着用于精确小胶质细胞调节的病毒工具的进步和大脑类器官模型的开发，我们准备阐明通过测序分析检测到的小胶质细胞亚群的功能作用，最终确定有价值的治疗靶点。