Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacol Biochem Behav. 2021 Jun;205:173190. doi: 10.1016/j.pbb.2021.173190. Epub 2021 Apr 15.
Depression is a psychiatric disorder with several comorbidities that has a complicated pathophysiology. Multiple mechanisms such as abnormal hypothalamic-pituitary adrenal (HPA) axis activity, neurotransmission (namely serotonin), and immune-inflammatory responses are involved in the pathophysiology of disease. In this study, we hypothesized that applying exercise (running wheel (RW) and treadmill (TM)) or fluoxetine (FLX) during adolescence could protect adult rats against the negative impact of early-life stress. To do this, we applied maternal separation stress (MS) to neonatal rats from postnatal day (PND) 2 to 14 and at PND 28, rats were divided into 8 experimental groups and were subjected to TM or RW or FLX treatment. After four weeks of physical activity or FLX treatment, at PND 64, behaviors were assessed by applying forced swimming test, sucrose preference test, open-field test, and elevated plus maze test. Serum cortiscosterone (CORT) levels and expression of genes associated with inflammatory factors (Il1β, Hmgb1, and Il6) and serotonergic systems (5-ht2c and 5-ht3a) were studies in the hippocampus (HIPP) and prefrontal cortex (PFC). Our results revealed that RW and FLX treatment during adolescence are capable of attenuating MS-induced depressive- and anxiety-like disorders in adult male rats. These effects were accompanied by the normalization of both serum CORT and the expression of genes in the HIPP and PFC. TM exercise in adolescence showed anxiolytic effects but failed to produce antidepressant-like effects. Results of this study suggest that voluntary physical activity during adolescence can reduce the negative effects of early-life stress through different mechanisms.
抑郁症是一种伴有多种合并症的精神障碍，其发病机制复杂。多种机制，如异常的下丘脑-垂体肾上腺（HPA）轴活动、神经递质（即 5-羟色胺）和免疫炎症反应，都参与了疾病的病理生理学过程。在这项研究中，我们假设在青春期进行运动（跑步轮（RW）和跑步机（TM））或氟西汀（FLX）治疗可以保护成年大鼠免受早期生活应激的负面影响。为此，我们对新生大鼠从出生后第 2 天（PND2）到第 14 天进行了母体分离应激（MS）处理，在 PND28 时，大鼠被分为 8 个实验组，并进行 TM 或 RW 或 FLX 治疗。在进行了四周的体育活动或 FLX 治疗后，在 PND64 时，通过强迫游泳试验、蔗糖偏好试验、旷场试验和高架十字迷宫试验评估行为。在海马体（HIPP）和前额叶皮层（PFC）中研究了与炎症因子（IL1β、Hmgb1 和 IL6）和 5-羟色胺能系统（5-ht2c 和 5-ht3a）相关的基因的血清皮质酮（CORT）水平和表达。我们的结果表明，青春期进行 RW 和 FLX 治疗能够减轻成年雄性大鼠 MS 诱导的抑郁和焦虑样障碍。这些作用伴随着 HIPP 和 PFC 中血清 CORT 和基因表达的正常化。青春期进行 TM 运动表现出抗焦虑作用，但未能产生抗抑郁样作用。这项研究的结果表明，青春期的自愿体育活动可以通过不同的机制减轻早期生活应激的负面影响。
