Miguel-Hidalgo José Javier
Dept. Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Explor Neuroprotective Ther. 2023;3(5):328-345. doi: 10.37349/ent.2023.00054. Epub 2023 Oct 31.
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.
星形胶质细胞不仅在突触神经传递、动作电位传播、代谢支持或神经可塑性及发育适应等方面发挥重要作用，以支持神经元功能。它们还会通过释放神经营养因子和其他分子，对周围神经元和少突胶质细胞的损伤或功能障碍做出反应，这些分子可增加所支持细胞的存活率，或有助于结构和分子修复机制。星形胶质细胞的神经保护反应性基于它们感知退化、代谢危机和结构损伤信号的能力，以及它们在局部递送特定分子以补救对其细胞伙伴分子和结构特征的威胁的能力。鉴于已知在情感障碍中会发生神经元和其他胶质细胞紊乱，星形胶质细胞对这些紊乱的反应性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胶质细胞传感装置涉及神经递质、嘌呤、细胞粘附分子和生长因子的受体。星形胶质细胞还与免疫系统一样，具有对神经元损伤时释放的细胞因子做出反应的能力。此外，在对特定信号的反应中，星形胶质细胞会释放独特的因子，如簇集蛋白或人胰岛素，这些因子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，进一步递送结构脂质、清除有毒代谢物、稳定渗透环境、使神经递质正常化、提供抗氧化保护、促进突触形成，并作为屏障来遏制各种有害信号，其中一些已在与情感障碍相关的脑区和相关动物模型中得到描述。由于激活星形胶质细胞的各种损伤信号已被牵连到情感障碍病因学的不同方面，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会为改善或补充现有的情感障碍药物和行为疗法提供额外的机会。
