Laboratory for Glia-Neuron Circuit Dynamics, RIKEN Center for Brain Science, Wako, Saitama, Japan.
Adv Neurobiol. 2024;39:137-163. doi: 10.1007/978-3-031-64839-7_6.
In the intricate landscape of neurophysiology, astrocytes have been traditionally cast as homeostatic cells; however, their mechanistic involvement in allostasis-particularly how they modulate the adaptive response to stress and its accumulative impact that disrupts cognitive functions and precipitates psychiatric disorders-is now starting to be unraveled. Here, we address the gap by positing astrocytes as crucial allostatic players whose molecular adaptations underlie cognitive flexibility in stress-related neuropsychiatric conditions. We review how astrocytes, responding to stress mediators such as glucocorticoid and epinephrine/norepinephrine, undergo morphological and functional transformations that parallel the maladaptive changes. Our synthesis of recent findings reveals that these glial changes, especially in the metabolically demanding prefrontal cortex, may underlie some of the neuropsychiatric mechanisms characterized by the disruption of energy metabolism and astrocytic networks, compromised glutamate clearance, and diminished synaptic support. We argue that astrocytes extend beyond their homeostatic role, actively participating in the brain's allostatic response, especially by modulating energy substrates critical for cognitive functions.
在神经生理学的复杂领域中，星形胶质细胞传统上被认为是具有维持内环境稳定作用的细胞；然而，它们在全身适应（allostasis）中的作用机制——特别是它们如何调节对压力的适应性反应及其累积影响，这种影响会破坏认知功能并引发精神疾病——现在正开始被揭示。在这里，我们通过假设星形胶质细胞是至关重要的全身适应参与者来填补这一空白，它们的分子适应是与应激相关的神经精神疾病中认知灵活性的基础。我们回顾了星形胶质细胞如何响应应激介质，如糖皮质激素和肾上腺素/去甲肾上腺素，经历形态和功能的转变，与适应不良的变化平行。我们对最近发现的综合分析表明，这些神经胶质细胞的变化，特别是在代谢需求较高的前额叶皮层，可能是一些神经精神机制的基础，这些机制的特征是能量代谢和星形胶质细胞网络的破坏、谷氨酸清除能力受损和突触支持减弱。我们认为，星形胶质细胞超越了其维持内环境稳定的作用，积极参与大脑的全身适应反应，特别是通过调节对认知功能至关重要的能量底物。
