Rehabilitation Department 2, The Second Clinical Medical College of Heilongjiang University of Chinese Medicine, 150000 Harbin, Heilongjiang, China.
Spine and Scoliosis Clinic, The Second Clinical Medical College of Heilongjiang University of Chinese Medicine, 150000 Harbin, Heilongjiang, China.
Actas Esp Psiquiatr. 2024 Oct;52(5):693-704. doi: 10.62641/aep.v52i5.1771.
Post-stroke depression (PSD) is a common complication, occurring in approximately one-third of these patients. The neurological symptoms of PSD affect patients' daily life and subsequent recovery. Analyzing the pathogenesis of post-stroke depression from a psychological perspective, it was found that PSD patients often feel despair and anxiety, and it is crucial to explore non-pharmacological ways to improve post-stroke depressive symptoms. A combination of exercise and rich environmental stimulation (RES) has been found effective in improving post-stroke depressive symptoms. Therefore, this study aimed to explore the effects of exercise and rich environmental stimulation on PSD in rats and their potential underlying mechanisms and to provide a theoretical basis for managing PSD.
The PSD rat model was constructed, and the depression-like behaviors of rats in each group were evaluated using the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Moreover, changes in the morphological behavior of rat hippocampus were observed using hematoxylin-eosin (HE) staining and Nissl staining. The expression levels of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hippocampus tissues were assessed using enzyme linked immunosorbent assay (ELISA), and the levels of tryptophan-related proteins were determined employing western blot analysis. Additionally, a kynurenine-3-monooxygenase (KMO) inhibitor was administered to the combined stimulation group, and the levels of tryptophan (TRP), 5-HT, kynurenine (KYN), 3-hydroxy-kynurenine (3-HK), and quinolinic acid (QA) were evaluated using liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS).
Treadmill exercise combined with rich environmental stimulation significantly reduced the immobility time in the FST (p < 0.01), increased the exploratory behavior in the OFT (p < 0.05), and increased the sucrose water consumption in the SPT (p < 0.01), indicating that the depression-like behavior was improved. Treadmill exercise combined with rich environmental stimulation also improved the shape of the damaged hippocampus and increased the number of neurons in the hippocampus. Additionally, treadmill exercise combined with rich environmental stimulation significantly increased the levels of 5-HT and NE in hippocampus tissues (p < 0.01) and decreased KMO protein level (p < 0.01). In the KMO inhibitor group, the neural function was efficiently restored, the levels of 3-HK, QA, and KMO in the hippocampus were substantially reduced (p < 0.01), and the expression level of 5-HT was increased (p < 0.01).
Exercise stimulation combined with enriched environmental stimuli alleviates post-stroke depression in rats, and the underlying mechanisms may be related to TRP/KYN/3-HK/QA excitotoxicity pathways and increased 5-hydroxytryptamine levels.
中风后抑郁（PSD）是一种常见的并发症，大约三分之一的中风患者会出现这种并发症。PSD 的神经症状会影响患者的日常生活和后续康复。从心理学角度分析 PSD 的发病机制，发现 PSD 患者常感到绝望和焦虑，因此，探索改善 PSD 症状的非药物方法至关重要。运动和丰富环境刺激（RES）的结合已被证明可有效改善 PSD。因此，本研究旨在探讨运动和丰富环境刺激对 PSD 大鼠的影响及其潜在的机制，并为 PSD 管理提供理论依据。
构建 PSD 大鼠模型，采用旷场试验（OFT）、糖水偏好试验（SPT）和强迫游泳试验（FST）评估各组大鼠的抑郁样行为。此外，采用苏木精-伊红（HE）染色和尼氏染色观察大鼠海马的形态学行为变化。采用酶联免疫吸附试验（ELISA）检测海马组织中 5-羟色胺（5-HT）和去甲肾上腺素（NE）的表达水平，采用 Western blot 分析检测色氨酸相关蛋白的表达水平。此外，在联合刺激组中给予犬尿氨酸-3-单加氧酶（KMO）抑制剂，并采用液相色谱-质谱/质谱（LC-MS/MS）检测色氨酸（TRP）、5-HT、犬尿氨酸（KYN）、3-羟基犬尿氨酸（3-HK）和喹啉酸（QA）的水平。
跑步机运动联合丰富环境刺激显著减少了 FST 中的不动时间（p<0.01），增加了 OFT 中的探索行为（p<0.05），并增加了 SPT 中的糖水消耗（p<0.01），表明抑郁样行为得到改善。跑步机运动联合丰富环境刺激还改善了受损海马的形状，并增加了海马神经元的数量。此外，跑步机运动联合丰富环境刺激显著增加了海马组织中 5-HT 和 NE 的水平（p<0.01），并降低了 KMO 蛋白水平（p<0.01）。在 KMO 抑制剂组中，神经功能得到有效恢复，海马中 3-HK、QA 和 KMO 的水平显著降低（p<0.01），5-HT 的表达水平升高（p<0.01）。
运动刺激联合丰富环境刺激可缓解 PSD 大鼠的抑郁，其潜在机制可能与 TRP/KYN/3-HK/QA 兴奋性毒性途径和 5-羟色胺水平升高有关。
