Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil.
Laboratory of Clinical and Experimental Pathophysiology, Postgraduate Program in Health Sciences, University of Southern Santa Catarina (UNISUL), Tubarão, SC, Brazil.
Behav Brain Res. 2021 May 21;406:113226. doi: 10.1016/j.bbr.2021.113226. Epub 2021 Mar 5.
Major depressive disorder (MDD) is one of the most prevalent forms of mental illness also affecting older adults. Recent evidence suggests a relationship between MDD and neurodegenerative diseases, including Parkinson's disease (PD). Individuals with PD have a predisposition to developing MDD, and both neurobiological conditions are associated with oxidative stress. Thus, we conducted this study to investigate depressive-like behavior and oxidative stress parameters using both animal models of PD and stress. Adult Wistar rats were subjected to chronic mild stress (CMS) protocol by 40 days and then it was used 6-hydroxydopamine (6-OHDA) as a model of PD, into the striatum. The experimental groups were: Control + Sham, Stress + Sham, Control+6-OHDA, and Stress+6-OHDA. Depressive like-behavior was evaluated by the forced swimming test (FST) and spontaneous locomotor activity by open-field test. Oxidative stress parameters were measured in the striatum, hippocampus, and prefrontal cortex (PFC). The results showed effects to increase immobility and decrease climbing times in the FST in Stress + Sham, Control+6-OHDA, and Stress+6-OHDA groups. The number of crossings and rearings were decreased in the Stress+6-OHDA group. The lipid peroxidation was increased in the PFC of Stress + Sham, and the hippocampus and striatum of Stress + Sham and Control+6-OHDA groups. Carbonyl protein levels increased in the PFC of Stress + Sham and striatum in Control+6-OHDA. Nitrite/Nitrate concentration was elevated in the PFC of Stress + Sham, in the hippocampus of Control+6-OHDA, the striatum of Stress + Sham, and Control+6-OHDA groups. Myeloperoxidase (MPO) activity was increased in the PFC and hippocampus of Stress + Sham and Control+6-OHDA groups. The activity of catalase decreased in the PFC of the Stress + Sham group. The activity of the superoxide dismutase (SOD) was decreased in the PFC of the Stress + Sham group, in the hippocampus of Stress + Sham and Control+6-OHDA groups, and the striatum of Control+6-OHDA group. These findings suggest that both stress and 6-OHDA induce depressive-like behavior and oxidative stress in the brain. The joining models have little evidence of the effects. Thus these findings suggest that other pathways are involved in the common point of the pathophysiology of PD and MDD.
重度抑郁症（MDD）是最常见的精神疾病之一，也会影响老年人。最近的证据表明，MDD 与神经退行性疾病之间存在关系，包括帕金森病（PD）。PD 患者易患 MDD，并且两种神经生物学状况都与氧化应激有关。因此，我们进行了这项研究，使用 PD 和应激的动物模型来研究抑郁样行为和氧化应激参数。成年 Wistar 大鼠接受 40 天的慢性轻度应激（CMS）方案，然后将 6-羟多巴胺（6-OHDA）用作 PD 模型，注入纹状体。实验组为：对照+假手术、应激+假手术、对照+6-OHDA 和应激+6-OHDA。通过强迫游泳试验（FST）评估抑郁样行为，通过旷场试验评估自发运动活动。在纹状体、海马体和前额叶皮层（PFC）中测量氧化应激参数。结果显示，应激+假手术、对照+6-OHDA 和应激+6-OHDA 组的 FST 中，不动时间增加，攀爬时间减少。应激+6-OHDA 组的穿越和后肢次数减少。应激+假手术组的 PFC 中脂质过氧化增加，应激+假手术和对照+6-OHDA 组的海马体和纹状体中脂质过氧化增加。PFC 中应激+假手术组和纹状体中对照+6-OHDA 组的羰基蛋白水平升高。PFC 中应激+假手术组、对照+6-OHDA 组的海马体、应激+假手术组和对照+6-OHDA 组的纹状体中，亚硝酸盐/硝酸盐浓度升高。髓过氧化物酶（MPO）活性在应激+假手术和对照+6-OHDA 组的 PFC 和海马体中增加。应激+假手术组 PFC 中的过氧化氢酶活性降低。应激+假手术组 PFC 中的超氧化物歧化酶（SOD）活性降低，应激+假手术和对照+6-OHDA 组的海马体和对照+6-OHDA 组的纹状体中 SOD 活性降低。这些发现表明，应激和 6-OHDA 都会在大脑中引起抑郁样行为和氧化应激。联合模型几乎没有证据表明有影响。因此，这些发现表明，PD 和 MDD 病理生理学的共同要点涉及其他途径。
