Sunnybrook Research Institute, Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Centre, Toronto, Canada; Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo, SP, Brazil.
Laboratory of Neuroscience, Hospital Sírio-Libanês, São Paulo, SP, Brazil.
Exp Neurol. 2023 Oct;368:114501. doi: 10.1016/j.expneurol.2023.114501. Epub 2023 Aug 8.
Treatment-resistant depression (TRD) is a debilitating condition that affects millions of individuals worldwide. Deep brain stimulation (DBS) has been widely used with excellent outcomes in neurological disorders such as Parkinson's disease, tremor, and dystonia. More recently, DBS has been proposed as an adjuvant therapy for TRD. To date, the antidepressant efficacy of DBS is still controversial, and its mechanisms of action remain poorly understood. Astrocytes are the most abundant cells in the nervous system. Once believed to be a "supporting" element for neuronal function, astrocytes are now recognized to play a major role in brain homeostasis, neuroinflammation and neuroplasticity. Because of its many roles in complex multi-factorial disorders, including TRD, understanding the effect of DBS on astrocytes is pivotal to improve our knowledge about the antidepressant effects of this therapy. In depression, the number of astrocytes and the expression of astrocytic markers are decreased. One of the potential consequences of this reduced astrocytic function is the development of aberrant glutamatergic neurotransmission, which has been documented in several models of depression-like behavior. Evidence from preclinical work suggests that DBS may directly influence astrocytic activity, modulating the release of gliotransmitters, reducing neuroinflammation, and altering structural tissue organization. Compelling evidence for an involvement of astrocytes in potential mechanisms of DBS derive from studies suggesting that pharmacological lesions or the inhibition of these cells abolishes the antidepressant-like effect of DBS. In this review, we summarize preclinical data suggesting that the modulation of astrocytes may be an important mechanism for the antidepressant-like effects of DBS.
治疗抵抗性抑郁症（TRD）是一种使人衰弱的疾病，影响着全球数百万人。深部脑刺激（DBS）已广泛应用于帕金森病、震颤和肌张力障碍等神经疾病，并取得了良好的效果。最近，DBS 被提议作为 TRD 的辅助治疗方法。迄今为止，DBS 的抗抑郁疗效仍存在争议，其作用机制仍知之甚少。星形胶质细胞是神经系统中最丰富的细胞。星形胶质细胞曾经被认为是神经元功能的“支持”元素，现在被认为在脑内稳态、神经炎症和神经可塑性中起主要作用。由于星形胶质细胞在包括 TRD 在内的复杂多因素疾病中具有许多作用，因此了解 DBS 对星形胶质细胞的影响对于提高我们对这种治疗方法的抗抑郁作用的认识至关重要。在抑郁症中，星形胶质细胞的数量和星形胶质细胞标志物的表达减少。这种星形胶质细胞功能降低的潜在后果之一是谷氨酸能神经传递的异常发展，这在几种类似抑郁症的行为模型中已有记录。临床前工作的证据表明，DBS 可能直接影响星形胶质细胞活性，调节神经递质的释放，减轻神经炎症，并改变结构组织的组织。有说服力的证据表明，星形胶质细胞参与了 DBS 的潜在机制，这些证据表明，药理学损伤或这些细胞的抑制作用消除了 DBS 的抗抑郁样作用。在这篇综述中，我们总结了临床前数据，表明星形胶质细胞的调节可能是 DBS 抗抑郁样作用的重要机制。
