Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome 00133, Italy.
Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome 00133, Italy; Synaptic Immunopathology Lab, IRCCS San Raffaele Pisana, Rome 00166, Italy.
Brain Behav Immun. 2021 Nov;98:13-27. doi: 10.1016/j.bbi.2021.08.212. Epub 2021 Aug 12.
Exercise is increasingly recommended as a supportive therapy for people with Multiple Sclerosis (pwMS). While clinical research has still not disclosed the real benefits of exercise on MS disease, animal studies suggest a substantial beneficial effect on motor disability and pathological hallmarks such as central and peripheral dysregulated immune response. The hippocampus, a core area for memory formation and learning, is a brain region involved in MS pathophysiology. Human and rodent studies suggest that the hippocampus is highly sensitive to the effects of exercise, the impact of which on MS hippocampal damage is still elusive. Here we addressed the effects of chronic voluntary exercise on hippocampal function and damage in experimental autoimmune encephalomyelitis (EAE), animal model of MS. Mice were housed in standard or wheel-equipped cages starting from the day of immunization and throughout the disease course. Although running activity was reduced during the symptomatic phase, exercise significantly ameliorated motor disability. Exercise improved cognition that was assessed through the novel object recognition test and the nest building in presymptomatic and acute stages of the disease, respectively. In the acute phase exercise was shown to prevent EAE-induced synaptic plasticity abnormalities in the CA1 area, by promoting the survival of parvalbumin-positive (PV+) interneurons and by attenuating inflammation. Indeed, exercise significantly reduced microgliosis in the CA1 area, the expression of tumour necrosis factor (TNF) in microglia and, to a lesser extent, the hippocampal level of interleukin 1 beta (IL-1β), previously shown to contribute to aberrant synaptic plasticity in the EAE hippocampus. Notably, exercise exerted a precocious and long-lasting mitigating effect on microgliosis that preceded its neuroprotective action, likely underlying the improved cognitive function observed in both presymptomatic and acute phase EAE mice. Overall, these data provide evidence that regular exercise improves cognitive function and synaptic and neuronal pathology that typically affect EAE/MS brains.
运动越来越被推荐为多发性硬化症患者（pwMS）的支持性治疗方法。虽然临床研究尚未揭示运动对多发性硬化症疾病的真正益处，但动物研究表明，运动对运动障碍和中央及外周失调的免疫反应等病理标志有实质性的有益影响。海马体是记忆形成和学习的核心区域，是与多发性硬化症病理生理学相关的脑区。人类和啮齿动物研究表明，海马体对运动的影响非常敏感，但运动对多发性硬化症海马体损伤的影响仍不清楚。在这里，我们研究了慢性自愿运动对实验性自身免疫性脑脊髓炎（EAE），多发性硬化症动物模型中海马体功能和损伤的影响。从免疫接种之日起，将小鼠饲养在标准笼或带轮笼中，并贯穿整个疾病过程。尽管在症状期运动活动减少，但运动显著改善了运动障碍。运动改善了认知，通过新物体识别测试和筑巢分别在疾病的前驱期和急性期进行评估。在急性期，运动被证明可以通过促进 PV+中间神经元的存活和减轻炎症来预防 EAE 引起的 CA1 区突触可塑性异常。事实上，运动显著减少了 CA1 区的小胶质细胞增生、小胶质细胞中肿瘤坏死因子（TNF）的表达，以及炎症程度较轻的海马白细胞介素 1β（IL-1β）水平，先前研究表明这些因子会导致 EAE 海马体中的异常突触可塑性。值得注意的是，运动对小胶质细胞增生的早期和长期缓解作用先于其神经保护作用，这可能是在 EAE 小鼠的前驱期和急性期观察到认知功能改善的原因。总之，这些数据为定期运动改善认知功能和通常影响 EAE/MS 大脑的突触和神经元病理学提供了证据。
