Abstract：
Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.
摘要：
出生后免疫激活（PIA）诱导大脑中持续的神经胶质激活，并在成人中引起各种神经病变。运动训练可以改善与压力相关的情绪障碍;然而，运动在生命早期免疫激活引起的精神疾病中的作用以及运动训练与神经胶质激活之间的关联尚不清楚.我们比较了不同运动强度对PIA模型的影响，包括高强度间歇训练（HIIT）和中等强度连续训练（MICT）。青少年小鼠的HIIT和MICT均抑制神经炎症，重塑的突触可塑性，并改善了成年后PIA诱发的情绪障碍。重要的是,HIIT在减少炎症和增加体重方面优于MICT。前额叶皮质（PFC）组织的RNA-seq揭示了基因表达模式，证实HIIT在通过KDM6B的表观遗传修饰改善脑胶质细胞活化方面比MICT更有效。我们调查了KDM6B的作用，一种特定的组蛋白赖氨酸去甲基化酶-组蛋白3赖氨酸27去甲基化酶,通过调节IL-4和脑源性神经营养因子（BDNF）的表达来抑制胶质细胞活化以对抗PIA诱导的抑郁和焦虑。总的来说,我们的数据支持HIIT通过调节KDM6B介导的表观遗传机制改善PIA诱导的心境障碍的观点,并表明HIIT在改善小鼠PIA心境障碍方面可能优于MICT.我们的发现为焦虑和抑郁障碍的治疗提供了新的见解。
