Effects of exercise on activation of microglia and astrocytes and neuronal apoptosis in depressed rats

doi:10.12307/2025.779

Abstract

Abstract: BACKGROUND: Cyclooxygenase-2 can significantly enhance depressive-like behavior in rats, and cyclooxygenase-2 inhibitors have antidepressant effects. Exercise can significantly reduce depressive-like behaviors in depressed patients. However, it is currently unclear whether exercise exerts an antidepressant effect by inhibiting cyclooxygenase-2.
OBJECTIVE: To reveal the effects of exercise on cyclooxygenase-2 expression, microglia and astrocyte activation, oxidative stress and neuronal apoptosis in depressed rats, as well as the possible molecular mechanisms.
METHODS: The rat model of depression was induced by chronic unpredictable mild stimulation. After modeling, the chronic unpredictable mild stimulation rats were randomly divided into stimulation group and wheel running group, with 10 rats in each group. In addition, 10 normal rats were selected as the control group. The rats in the control group and stimulation group did not exercise. The rats in the wheel running group performed forced wheel running for a total of 4 weeks. Depressive-like behavior was evaluated by sucrose preference test. Hippocampal cyclooxygenase-2 expression was detected by immunofluorescence staining. The expression of cyclooxygenase-2, Iba-1, CD11b, CD45, glial fibrillary acid protein, Bcl-2, Bax, and cleaved caspase-3 proteins in the hippocampus was detected by western blot analysis. The cyclooxygenase-2 mRNA level in the hippocampus was detected by RT-PCR. The activities of antioxidant enzymes in hippocampal tissue homogenates were determined using kits.
RESULTS AND CONCLUSION: Compared with stimulation group, sucrose consumption was increased; cyclooxygenase-2 expression in hippocampus was decreased; superoxide dismutase, catalase, and glutathione peroxidase levels in hippocampus were increased; malonaldehyde level was decreased; Iba1, CD11b, and CD45 protein expression levels in hippocampus were decreased, and glial fibrillary acid protein level in hippocampus was decreased. Bcl-2 protein expression levels in the hippocampus were increased, while Bax and cleaved caspase-3 levels were decreased in wheel running group (P < 0.05). This study showed that wheel running could reduce depressive-like behavior by inhibiting the expression of cyclooxygenase-2 in the hippocampus of chronic unpredictable mild stimulation rats. In addition, wheel running can exert antidepressant effects by inhibiting microglia and astrocyte activation, oxidative stress, and neuronal apoptosis in the hippocampus.

Key words: depression, wheel running, chronic unpredictable mild stimulation, cyclooxygenase-2, oxidative stress, neuronal apoptosis, microglia, astrocyte, engineered tissue construction

CLC Number:

Du Juan, Zhang Yi, Hao Quanshui. Effects of exercise on activation of microglia and astrocytes and neuronal apoptosis in depressed rats[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(29): 6243-6248.

Figures/Tables 5

2.1 实验动物数量分析造模成功的20只大鼠及正常对照组10只大鼠全部完成实验进入结果分析。 2.2 转轮运动改善了抑郁大鼠模型的抑郁样行为与对照组相比，刺激组大鼠的蔗糖消耗量显著减少(P < 0.05)。表明慢性不可预测温和刺激大鼠缺乏快感，表现出抑郁的核心症状。然而，与刺激组相比，转轮运动组的蔗糖消耗量显著增加(P < 0.05)，见图1。 2.3 转轮运动抑制了抑郁大鼠模型海马中环加氧酶2的表达使用RT-PCR、Western blot和免疫荧光染色测定抑郁大鼠模型海马内的环加氧酶2表达。与对照组相比，在刺激组大鼠海马内环加氧酶2水平显著增加(P < 0.05)；与刺激组相比，转轮运动组大鼠海马内的环加氧酶2表达显著降低(P < 0.05)，见图2。 2.4 转轮运动抑制了抑郁大鼠模型海马的氧化应激抑郁症通常伴有特定大脑区域的神经元损伤以及过量产生的活性氧，活性氧可导致衰老或细胞死亡。分析表明，与对照组相比，慢性不可预测温和刺激大鼠海马内抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性显著降低(P < 0.05)，见图3。与对照组相比，刺激组大鼠的海马内观察到氧化应激产物丙二醛的水平升高(P < 0.05)；与刺激组相比，转轮运动组大鼠海马内的超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶水平显著增加，而丙二醛水平显著降低(P < 0.05)。 2.5 转轮运动抑制了抑郁大鼠模型海马的神经胶质细胞活化与对照组相比，刺激组大鼠海马的Iba1蛋白表达水平显著增加(P < 0.05)，并且小胶质细胞标记物CD11b和CD45蛋白表达水平显著增加(P < 0.05)，见图4。这些结果表明，慢性不可预测温和刺激诱导了大鼠海马内的小胶质细胞活化。与刺激组相比，转轮运动组大鼠海马内的Iba1、CD11b和CD45蛋白表达水平显著降低(P < 0.05)。星形胶质细胞的激活在神经炎症反应中也起着至关重要的作用。蛋白质印迹分析表明，刺激组大鼠海马胶质纤维酸性蛋白水平显著增加(P < 0.05)；与刺激组相比，转轮运动组大鼠海马内的胶质纤维酸性蛋白水平显著降低(P < 0.05)，见图4。 2.6 转轮运动抑制了抑郁大鼠模型海马中神经细胞凋亡过量产生活性氧会导致细胞死亡或衰老。研究进一步检测了转轮运动是否可以调节慢性不可预测温和刺激大鼠的神经凋亡，与对照组相比，刺激组大鼠的海马内Bcl-2的蛋白表达水平显著降低，而Bax和cleaved caspase-3显著增加(P < 0.05)；与刺激组相比，转轮运动组大鼠海马内的Bcl-2的蛋白表达水平显著升高，Bax和cleaved caspase-3降低(P < 0.05)，见图5。"

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