Klein Caroline Peres, Hoppe Juliana Bender, Saccomori André Brum, Gindri Dos Santos Bernardo, August Pauline Maciel, Klein Isadora Peres, Crestani Mariana Scortegagna, Bifi Felippo, Hözer Régis Mateus, Navas Plácido, Salbego Christianne Gazzana, Matté Cristiane
Programa de Pós-Graduação em Ciências Biológicas - Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
J Dev Orig Health Dis. 2020 Oct;11(5):521-532. doi: 10.1017/S2040174420000562. Epub 2020 Jun 23.
The Developmental Origins of Health and Disease (DOHaD) states that intrauterine maternal environment influences postnatal life by programming offspring's metabolism. Intrauterine milieu induced by exercise during pregnancy promotes long-lasting benefits to the offspring's health and seems to offer some resistance against chronic diseases in adult life. Alzheimer's disease is a public health concern with limited treatment options. In the present study, we assessed the potential of maternal exercise during pregnancy in long-term programming of young adult male rat offspring's cerebellar metabolism in conferring neuroprotection against amyloid-β (Aβ) neurotoxicity. Female Wistar rats were submitted to a swimming protocol 1 week prior mating and throughout pregnancy (five sessions/a week lasting 30 min). Aβ oligomers were infused bilaterally in the brain ventricles of 60-day-old male offspring. Fourteen days after surgery, we measured parameters related to redox state, mitochondrial function, and the immunocontent of proteins related to synaptic function. We found that maternal exercise during pregnancy attenuated several parameters in the offspring's male rat cerebellum, such as the reactive species rise, the increase of inducible nitric oxide synthase immunocontent and tau phosphorylation induced by Aβ oligomers, increased mitochondrial fission indicated by dynamin-related protein 1 (DRP1), and protein oxidation identified by carbonylation. Strikingly, we find that maternal exercise promotes changes in the rat offspring's cerebellum that are still evident in young adult life. These favorable neurochemical changes in offspring's cerebellum induced by maternal exercise may contribute to a protective phenotype against Aβ-induced neurotoxicity in young adult male rat offspring.
健康与疾病的发育起源（DOHaD）理论指出，子宫内的母体环境通过对后代新陈代谢进行编程来影响产后生活。孕期运动所诱导的子宫内环境对后代健康具有持久的益处，并且似乎能为成年后的慢性疾病提供一定的抵抗力。阿尔茨海默病是一个公共卫生问题，治疗选择有限。在本研究中，我们评估了孕期母体运动对年轻成年雄性大鼠后代小脑代谢进行长期编程的潜力，以及其对淀粉样蛋白-β（Aβ）神经毒性的神经保护作用。雌性Wistar大鼠在交配前1周及整个孕期接受游泳训练（每周5次，每次30分钟）。将Aβ寡聚体双侧注入60日龄雄性后代的脑室。手术后14天，我们测量了与氧化还原状态、线粒体功能以及与突触功能相关的蛋白质免疫含量有关的参数。我们发现，孕期母体运动减轻了后代雄性大鼠小脑中的几个参数变化，例如活性物质增加、Aβ寡聚体诱导的诱导型一氧化氮合酶免疫含量增加和tau蛋白磷酸化，动力蛋白相关蛋白1（DRP1）显示的线粒体裂变增加以及羰基化所确定的蛋白质氧化。令人惊讶的是，我们发现母体运动促进了大鼠后代小脑中的变化，这些变化在年轻成年期仍然明显。孕期母体运动在后代小脑中诱导的这些有利的神经化学变化可能有助于在年轻成年雄性大鼠后代中形成针对Aβ诱导的神经毒性的保护表型。
