Laboratory of Physiology, Pharmacology and Psychopathology, Federal University of Southern Frontier, Chapecó, SC, 89815-899, Brazil.
Laboratory of Translational Psychiatry, University of Southern Santa Catarina, Criciúma, SC, Brazil.
Mol Neurobiol. 2019 Dec;56(12):8323-8335. doi: 10.1007/s12035-019-01670-1. Epub 2019 Jun 21.
Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with varied prognosis, chronic course, and duration of illness with reduced quality of life. One factor that significantly contributes to the relevant disease burden of MDD is the heterogeneous treatment response patients experience with current treatment options. A variety of experimental protocols in humans and animals have highlighted that inflammation and neuroinflammation are relevant biological factors that interact with external stimuli and neurophysiological mechanisms, and can trigger MDD. It is well established that exercise is efficacious in treating mild to moderate depression with response rates comparable to mainstream therapies such as antidepressant medication and cognitive behavioral therapy. Several studies have shown that physical exercise is beneficial for a range of chronic diseases. Indeed, physical exercise can promote molecular changes that swerve a chronic pro-inflammatory state to an anti-inflammatory state in both periphery and central nervous system. The changes caused by physical exercise include an increase in PGC1α gene expression, a transcriptional co-activator involved in reducing the synthesis and releasing of pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines. PGC1α changes the metabolism of kynurenine towards, and, in turn, it reduces glutamatergic neurotoxicity. Moreover, some studies have shown that physical exercise promotes alterations in the circuitry of monoaminergic neurotransmission, at least in some aspects, through the effects on the release of proinflammatory cytokines. This review will highlight the effects of physical exercise as therapy and its relation with the biological mechanisms involved in the pathophysiology of MDD, with particular emphasis in the interactions among physical exercise, hypothalamic-pituitary-adrenal (HPA) axis, neuroinflammation, and with the neurotransmitters underlying the main brain circuits involved in the MDD.
重度抑郁症（MDD）是一种常见的精神疾病，其预后、慢性病程和疾病持续时间各不相同，生活质量降低。导致 MDD 相关疾病负担的一个重要因素是患者对当前治疗选择的治疗反应存在异质性。人类和动物的各种实验方案强调，炎症和神经炎症是与外部刺激和神经生理机制相互作用并可能引发 MDD 的相关生物学因素。运动在治疗轻度至中度抑郁症方面是有效的，其反应率可与抗抑郁药和认知行为疗法等主流疗法相媲美，这一点已得到充分证实。多项研究表明，体育锻炼有益于一系列慢性疾病。事实上，体育锻炼可以促进分子变化，使慢性促炎状态向外周和中枢神经系统的抗炎状态转变。体育锻炼引起的变化包括 PGC1α 基因表达增加，PGC1α 是一种参与减少促炎细胞因子合成和释放的转录共激活因子，以及抗炎细胞因子增加。PGC1α 改变色氨酸向犬尿氨酸的代谢，进而减少谷氨酸的神经毒性。此外，一些研究表明，体育锻炼通过影响促炎细胞因子的释放，至少在某些方面促进单胺能神经递质传递回路的改变。本综述将重点介绍运动作为治疗方法的效果及其与 MDD 病理生理学中涉及的生物学机制之间的关系，特别强调运动、下丘脑-垂体-肾上腺（HPA）轴、神经炎症以及与 MDD 相关的主要大脑回路的神经递质之间的相互作用。
