Physical Exercise and Neuroinflammation in Major Depressive Disorder
Physical Exercise and Neuroinflammation in Major Depressive Disorder
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重度抑郁症的体育锻炼与神经炎症
DOI：
10.1007/s12035-019-01670-1
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发表时间：
2019-12-01
影响因子：
5.1
通讯作者：
Reus, Gislaine Z.
中科院分区：
文献类型：
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作者：
Ignacio, Zuleide M.;da Silva, Renato S.;Reus, Gislaine Z.
重性抑郁障碍（MDD）是一种流行的精神疾病，与不同的预后，慢性病程，疾病的持续时间和生活质量下降。显著导致MDD相关疾病负担的一个因素是患者在当前治疗方案中经历的异质性治疗应答。在人类和动物中的各种实验方案已经强调，炎症和神经炎症是与外部刺激和神经生理机制相互作用的相关生物学因素，并且可以触发MDD。众所周知，运动在治疗轻度至中度抑郁症方面是有效的，其反应率与抗抑郁药物和认知行为疗法等主流疗法相当。一些研究表明，体育锻炼对一系列慢性疾病有益。事实上，体育锻炼可以促进分子变化，使外周和中枢神经系统的慢性促炎状态转向抗炎状态。体育锻炼引起的变化包括PGC 1 α基因表达的增加，这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，以及抗炎细胞因子的增加。PGC 1 α改变犬尿氨酸的代谢，进而降低多巴胺能神经毒性。此外，一些研究表明，体育锻炼促进单胺能神经传递回路的改变，至少在某些方面，通过对促炎细胞因子释放的影响。这篇综述将突出体育锻炼作为治疗的效果及其与MDD病理生理学中所涉及的生物学机制的关系，特别强调体育锻炼、下丘脑-垂体-肾上腺（HPA）轴、神经炎症之间的相互作用，以及与MDD中所涉及的主要脑回路相关的神经递质。
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 PGC1 alpha gene expression, a transcriptional co-activator involved in reducing the synthesis and releasing of pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines. PGC1 alpha 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.