Ramos-Jiménez Arnulfo, Rubio-Valles Mariazel, Ramos-Hernández Javier A, González-Rodríguez Everardo, Moreno-Brito Verónica
Institute of Biomedical Sciences, Autonomous University of Ciudad Juarez, Ciudad Juarez Campus, Chihuahua 32310, Mexico.
Faculty of Physical Culture Sciences, Autonomous University of Chihuahua, University Circuit, Campus II, Chihuahua 31125, Mexico.
Int J Mol Sci. 2025 Sep 6;26(17):8697. doi: 10.3390/ijms26178697.
Mitochondrial dysfunction is a key factor in the pathophysiology of major depressive disorder (MDD) and treatment-resistant depression (TRD), connecting oxidative stress, neuroinflammation, and reduced neuroplasticity. Physical exercise induces specific mitochondrial changes linked to improvements in mental health. The aim of this paper was to examine emerging evidence regarding the effects of physical exercise on mitochondrial function and treatment-resistant depression, highlighting the clinical importance of the use of mitochondrial biomarkers to personalize exercise prescriptions for patients with depression, particularly those who cannot tolerate standard treatments. Physical exercise improves mitochondrial function, enhances biogenesis and neuroplasticity, and decreases oxidative stress and neuroinflammation. Essential signaling pathways, including brain-derived neurotrophic factor, AMP-activated protein kinase, active peroxisome proliferator-activated receptor-γ coactivator-1α, and Ca/calmodulin-dependent protein kinase, support these effects. Most studies have concentrated on the impact of low- and moderate-intensity aerobic exercise on general health. However, new evidence suggests that resistance exercise and high-intensity interval training also promote healthy mitochondrial adaptations, although the specific exercise intensity required to achieve this goal remains to be determined. There is strong evidence that exercise is an effective treatment for MDD, particularly for TRD, by promoting specific mitochondrial adaptations. However, key gaps remain in our understanding of the optimal exercise dose and which patient subgroups are most likely to benefit from it (Graphical Abstract).
线粒体功能障碍是重度抑郁症（MDD）和难治性抑郁症（TRD）病理生理学中的关键因素，它将氧化应激、神经炎症和神经可塑性降低联系起来。体育锻炼会引发与心理健康改善相关的特定线粒体变化。本文的目的是研究关于体育锻炼对线粒体功能和难治性抑郁症影响的新证据，强调使用线粒体生物标志物为抑郁症患者（尤其是那些无法耐受标准治疗的患者）制定个性化运动处方的临床重要性。体育锻炼可改善线粒体功能，增强生物合成和神经可塑性，并降低氧化应激和神经炎症。包括脑源性神经营养因子、AMP激活的蛋白激酶、活性过氧化物酶体增殖物激活受体γ共激活因子1α和钙/钙调蛋白依赖性蛋白激酶在内的重要信号通路支持这些作用。大多数研究都集中在低强度和中等强度有氧运动对总体健康的影响上。然而，新证据表明，抗阻运动和高强度间歇训练也能促进线粒体产生有益的适应性变化，尽管实现这一目标所需的具体运动强度仍有待确定。有强有力的证据表明，运动是治疗MDD的有效方法，尤其是对TRD，因为它能促进线粒体产生特定的适应性变化。然而，在我们对最佳运动剂量以及哪些患者亚组最可能从中受益的理解方面，仍存在关键差距（图摘要）。
