Neuroprotective astroglial response to neural damage and its relevance to affective disorders.
Neuroprotective astroglial response to neural damage and its relevance to affective disorders.
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DOI：
10.37349/ent.2023.00054
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发表时间：
2023-10
期刊：
影响因子：
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通讯作者：
J. Miguel-Hidalgo
中科院分区：
文献类型：
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作者：
J. Miguel-Hidalgo
星形胶质细胞不仅支持神经元的功能，在突触神经传递、动作电位传播、代谢支持或神经再生和发育适应中发挥重要作用。它们还通过释放神经营养因子和其他分子来应对周围神经元和少突胶质细胞的损伤或功能障碍，这些分子可以增加被支持细胞的存活率，或有助于结构和分子修复的机制。星形胶质细胞的神经保护反应是基于它们感知退化、代谢危险和结构损伤的信号的能力，以及它们局部递送特定分子的能力来补救对其细胞伴侣的分子和结构特征的威胁。就已知的情感障碍中神经元和其他胶质细胞障碍的程度而言，星形胶质细胞对这些障碍的反应可能有助于更好地理解星形胶质细胞在情感障碍中所起的作用。支持这些反应的星形细胞感受器涉及神经递质、嘌呤、细胞黏附分子和生长因子的受体。星形胶质细胞也与免疫系统一样，对神经元损伤时释放的细胞因子做出反应。此外，在对特定信号的反应中，星形胶质细胞释放独特的因素，如聚集素或人蛋白，已被证明具有强大的神经保护作用。星形胶质细胞整合上述信号以进一步传递结构脂类，清除有毒代谢物，稳定渗透环境，正常化神经递质，提供抗氧化保护，促进突触形成，并充当包含各种有害信号的屏障，其中一些已在与情感障碍和相关动物模型相关的大脑区域被描述。由于激活星形胶质细胞的各种伤害性信号与情感性精神障碍的发病机制有关，特别是与抑郁症的诊断有关，增强相应的星形胶质细胞神经保护反应可能为改善或补充现有的情感性精神障碍的药物和行为治疗提供额外的机会。
Astrocytes not only support neuronal function with essential roles in synaptic neurotransmission, action potential propagation, metabolic support, or neuroplastic and developmental adaptations. They also respond to damage or dysfunction in surrounding neurons and oligodendrocytes by releasing neurotrophic factors and other molecules that increase the survival of the supported cells or contribute to mechanisms of structural and molecular restoration. The neuroprotective responsiveness of astrocytes is based on their ability to sense signals of degeneration, metabolic jeopardy and structural damage, and on their aptitude to locally deliver specific molecules to remedy threats to the molecular and structural features of their cellular partners. To the extent that neuronal and other glial cell disturbances are known to occur in affective disorders, astrocyte responsiveness to those disturbances may help to better understand the roles astrocytes play in affective disorders. The astrocytic sensing apparatus supporting those responses involves receptors for neurotransmitters, purines, cell adhesion molecules and growth factors. Astrocytes also share with the immune system the capacity of responding to cytokines released upon neuronal damage. In addition, in responses to specific signals astrocytes release unique factors such as clusterin or humanin that have been shown to exert potent neuroprotective effects. Astrocytes integrate the signals above to further deliver structural lipids, removing toxic metabolites, stabilizing the osmotic environment, normalizing neurotransmitters, providing anti-oxidant protection, facilitating synaptogenesis and acting as barriers to contain varied deleterious signals, some of which have been described in brain regions relevant to affective disorders and related animal models. Since various of the injurious signals that activate astrocytes have been implicated in different aspects of the etiopathology of affective disorders, particularly in relation to the diagnosis of depression, potentiating the corresponding astrocyte neuroprotective responses may provide additional opportunities to improve or complement available pharmacological and behavioral therapies for affective disorders.