Long-term plasticity of astrocytic phenotypes and their control by neurons in health and disease.
Long-term plasticity of astrocytic phenotypes and their control by neurons in health and disease.
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DOI：
10.1042/ebc20220090
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发表时间：
2023-03-03
影响因子：
6.4
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中科院分区：
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即使从细胞生物学的角度来看，大脑也是一个复杂的器官。神经元网络嵌入在多种特殊细胞类型的密集环境中，包括几种类型的血管细胞、免疫细胞和大胶质细胞。将每个细胞视为高度复杂机器中的一个小齿轮本身就过于简单化了。它们不仅在功能上相互耦合以使大脑能够运转，而且每种细胞类型的功能本身在发育、成熟以及疾病中都相互影响。星形胶质细胞是一种大胶质细胞，占据了人类前脑的很大一部分。它们通过无数的稳态功能（包括维持氧化还原平衡、离子梯度、神经递质清除和生物能量支持）在整个生命周期维持功能性神经元回路中发挥着关键作用。越来越明显的是，星形胶质细胞执行这些和其他神经支持作用的能力并不是固定的，而是受到来自神经元本身的信号的调节，无论是在健康的大脑中，还是对神经元衍生疾病病理学的反应。在这里，我们回顾神经元长期控制星形胶质细胞特性的机制，以改变其发育和成熟过程中的稳态能力。我们的工作假设是，这些信号旨在改变和维持局部星形胶质细胞的稳态能力，以满足附近神经元的需求。人们正在发现可以控制健康星形胶质细胞表型核心方面的外部信号的知识，这提出了一个问题：是否可以利用这些知识来促进脑部疾病中星形胶质细胞介导的神经支持。
The brain is a complex organ even when viewed from a cell biological perspective. Neuronal networks are embedded in a dense milieu of diverse and specialised cell types, including several types of vascular, immune, and macroglial cells. To view each cell as a small cog in a highly complex machine is itself an oversimplification. Not only are they functionally coupled to enable the brain to operate, each cell type’s functions are themselves influenced by each other, in development, maturity, and also in disease. Astrocytes are a type of macroglia that occupy a significant fraction of the human forebrain. They play a critical role in sustaining functional neuronal circuits across the lifespan through myriad homeostatic functions including the maintenance of redox balance, ionic gradients, neurotransmitter clearance, and bioenergetic support. It is becoming apparent that astrocytes’ capacity to carry out these and other neurosupportive roles is not fixed, but is regulated by signals coming from the neurons themselves, both in the healthy brain but also in response to neuron-derived disease pathology. Here, we review mechanisms by which neurons control the properties of astrocytes long term in order to alter their homeostatic capacity both in development and maturity. Our working hypothesis is that these signals are designed to change and maintain the homeostatic capacity of local astrocytes to suit the needs of nearby neurons. Knowledge of the external signals that can control core aspects of a healthy astrocytic phenotype are being uncovered, raising the question as to whether this knowledge can be harnessed to promote astrocyte-mediated neurosupport in brain disorders.