Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China; Faculty of Physical Education and Health, Huaihua University, China.
Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha 410012, China.
Physiol Behav. 2024 Nov 1;286:114676. doi: 10.1016/j.physbeh.2024.114676. Epub 2024 Aug 23.
Microglia activation-induced neuroinflammation is a risk factor for cognitive dysfunction in the hippocampus during the early stages of neurodegenerative diseases. Exercise is an intrinsic remedy that plays a crucial role in enhancing the survival of neurons and reducing neuroinflammation in the brain. Among these theories, alterations in intracellular signaling pathways associated with neuronal growth and inflammation have been emphasized. Based on these observations and recent evidence demonstrating the beneficial effects of exercise on suppressing brain inflammation in the elderly, we examined cellular signaling pathways in the hippocampal formation of D-galactose-induced accelerated aging mice that underwent 8 weeks of treadmill exercise. To accomplish this, we utilized immunohistochemistry and Western blotting to detect the expression of hippocampal proteins, and qPCR to detect the expression of mRNA. We found that aerobic exercise significantly promoted the survival of hippocampal neurons, inhibited microglia activation, and decreased the expression of inflammatory cytokines TNF-α, IL-1α, IL-1β, and chemokines CXCL-1, CXCR-2 in D-galactose model mice. Furthermore, exercise contributed to decreasing the microglia activation marker Iba1-positive cell count and average optical density and increasing the number of NeuN-immunopositive cells. Exercise also reduced RIPK1 and MAP3K5 expression in the hippocampus. Surprisingly, aerobic exercise significantly decreased the expression ratios of p-p65/p65, p-IκBα/IκBα, and p-JNK/JNK. Therefore, we hypothesized that exercise has an anti-inflammatory effect on the hippocampus of mice in the D-galactose-induced aging model. This effect may be attributed to the ability of aerobic exercise to down-regulate the RIPK1-mediated NF-κB and JNK pathways.
小胶质细胞激活诱导的神经炎症是神经退行性疾病早期海马认知功能障碍的一个风险因素。运动是一种内在的治疗方法，在增强神经元存活和减少大脑神经炎症方面起着至关重要的作用。在这些理论中，与神经元生长和炎症相关的细胞内信号通路的改变受到了重视。基于这些观察结果和最近的证据表明运动对抑制老年人大脑炎症的有益作用，我们检查了接受 8 周跑步机运动的 D-半乳糖诱导加速衰老小鼠海马形成中的细胞信号通路。为此，我们使用免疫组织化学和 Western blot 检测海马蛋白的表达，并使用 qPCR 检测 mRNA 的表达。我们发现，有氧运动显著促进了海马神经元的存活，抑制了小胶质细胞的激活，并降低了 D-半乳糖模型小鼠中炎症细胞因子 TNF-α、IL-1α、IL-1β 和趋化因子 CXCL-1、CXCR-2 的表达。此外，运动有助于减少小胶质细胞激活标志物 Iba1 阳性细胞计数和平均光密度，并增加 NeuN 免疫阳性细胞的数量。运动还降低了海马中的 RIPK1 和 MAP3K5 表达。令人惊讶的是，有氧运动显著降低了 p-p65/p65、p-IκBα/IκBα 和 p-JNK/JNK 的表达比率。因此，我们假设运动对 D-半乳糖诱导的衰老模型小鼠的海马具有抗炎作用。这种作用可能归因于有氧运动对 RIPK1 介导的 NF-κB 和 JNK 通路的下调作用。
