Ghinea Flavia Semida, Ionică Marius Viorel, Liliac Ilona Mihaela, Pătru Simion, Olaru Denisa Greta, Popa-Wagner Aurel
Experimental Research Center for Normal and Pathological Aging, University of Medicine and Medicine Craiova, Romania.
Department of Histology, University of Medicine and Medicine Craiova, Romania.
Curr Health Sci J. 2024 Jan-Mar;50(1):133-150. doi: 10.12865/CHSJ.50.01.17. Epub 2024 Mar 31.
Microglial cells play a pivotal role in the brain's health and operation through all stages of life and in the face of illness. The contributions of microglia during the developmental phase of the brain markedly contrast with their contributions in the brain of adults after injury. Enhancing our understanding of the pathological mechanisms that involve microglial activity in brains as they age and in cerebrovascular conditions is crucial for informing the creation of novel therapeutic approaches. In this work we provide results on microglia transcriptomics in the juvenile vs injured adult brain and its impact on adult brain regeneration after cerebral ischemia. During fetal brain development, microglia cells are involved in gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis, neurogenesis and synaptic reorganization by engulfing neuronal extensions. Within the mature, intact brain, microglial cells exhibit reduced movement of their processes in response to minimal neuronal activity, while they continuously monitor their surroundings and clear away cellular debris. Following a stroke in the adult brain, inflammation, neurodegeneration, or disruptions in neural equilibrium trigger alterations in both the genetic blueprint and the structure and roles of microglia, a state often described as "activated" microglia. Such genetic shifts include a notable increase in the pathways related to phagosomes, lysosomes, and the presentation of antigens, coupled with a rise in the expression of genes linked to cell surface receptors. We conclude that a comparison of microglia transcriptomic activity during brain development and post-stroke adult brain might provide us with new clues about how neurodegeneration occurs in the adult brain. This information could very useful to develop drugs to slow down or limit the post-stroke pathology and improve clinical outcome.
小胶质细胞在生命的各个阶段以及面对疾病时，对大脑的健康和运作起着关键作用。小胶质细胞在大脑发育阶段的作用与它们在成人大脑受伤后的作用形成了显著对比。加深我们对大脑衰老和脑血管疾病中涉及小胶质细胞活动的病理机制的理解，对于开发新的治疗方法至关重要。在这项工作中，我们提供了关于幼年与受伤成年大脑中小胶质细胞转录组学的结果，以及它对脑缺血后成年大脑再生的影响。在胎儿大脑发育过程中，小胶质细胞通过吞噬神经元延伸参与神经胶质生成、血管生成、轴突生长、突触形成、神经发生和突触重组。在成熟、完整的大脑中，小胶质细胞的突起运动因最小限度的神经元活动而减少，同时它们持续监测周围环境并清除细胞碎片。在成人大脑中风后，炎症、神经退行性变或神经平衡的破坏会触发小胶质细胞的基因蓝图以及结构和功能的改变，这种状态通常被描述为“活化”的小胶质细胞。这种基因变化包括与吞噬体、溶酶体和抗原呈递相关的途径显著增加，以及与细胞表面受体相关的基因表达上升。我们得出结论，比较大脑发育过程中和中风后成年大脑中的小胶质细胞转录组活性，可能会为我们提供关于成人大脑中神经退行性变如何发生的新线索。这些信息对于开发药物以减缓或限制中风后的病理变化并改善临床结果可能非常有用。
