Department of Exercise Physiology, Payame Noor University, Tehran PO Box 3697-19395, Iran.
Department of Exercise Physiology, Tehran Central Branch, Islamic Azad University, Tehran, Iran.
Physiol Behav. 2023 Oct 1;269:114264. doi: 10.1016/j.physbeh.2023.114264. Epub 2023 Jun 7.
Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders in children. No effective therapeutic strategies are currently approved to treat or manage core symptoms of autism. Active lifestyles and physical activity are closely associated with health and quality of life during childhood and adulthood. This study aimed to evaluate whether swimming exercise during adolescence can prevent the development of cognitive dysfunction and stress-related disorders in prenatally VPA-exposed mice offspring. Pregnant mice received VPA, afterwards, offspring were subjected to swimming exercise. We assessed neurobehavioral performances and inflammatory cytokines (interleukin-(IL)6, tumor-necrosis-factor-(TNF)α, interferon-(IFN)γ, and IL-17A) in the hippocampus and prefrontal cortex of offspring. Prenatal VPA treatment increased anxiety-and anhedonia-like behavior and decreased social behavior in male and female offspring. Prenatal VPA exposure also increased behavioral despair and reduced working and recognition memory in male offspring. Although prenatal VPA increased hippocampal IL-6 and IFN-γ, and prefrontal IFN-γ and IL-17 in males, it only increased hippocampal TNF-α and IFN-γ in female offspring. Adolescent exercise made VPA-treated male and female offspring resistant to anxiety-and anhedonia-like behavior in adulthood, whereas it only made VPA-exposed male offspring resistant to behavioral despair, social and cognitive deficits in adulthood. Exercise reduced hippocampal IL-6, TNF-α, IFN-γ, and IL-17, and prefrontal IFN-γ and IL-17 in VPA-treated male offspring, whereas it reduced hippocampal TNF-α and IFN-γ in VPA-treated female offspring. This study suggests that adolescent exercise may prevent the development of stress-related symptoms, cognitive deficits, and neuroinflammation in prenatally VPA-exposed offspring mice.
丙戊酸（VPA）在怀孕期间的治疗是儿童自闭症谱系障碍、认知缺陷和与应激相关障碍发展的一个风险因素。目前没有有效的治疗策略被批准用于治疗或管理自闭症的核心症状。积极的生活方式和体育活动与儿童期和成年期的健康和生活质量密切相关。本研究旨在评估青春期游泳运动是否可以预防产前 VPA 暴露的小鼠后代认知功能障碍和与应激相关障碍的发展。怀孕的老鼠接受 VPA 治疗，之后，后代接受游泳运动。我们评估了后代海马体和前额叶皮层的神经行为表现和炎症细胞因子（白细胞介素-(IL)6、肿瘤坏死因子-(TNF)α、干扰素-(IFN)γ 和 IL-17A）。产前 VPA 处理增加了雄性和雌性后代的焦虑和快感缺失样行为，并减少了社交行为。产前 VPA 暴露还增加了雄性后代的行为绝望，并降低了工作和识别记忆。尽管产前 VPA 增加了雄性后代海马体中的 IL-6 和 IFN-γ，以及前额叶中的 IFN-γ 和 IL-17，但它仅增加了雌性后代海马体中的 TNF-α 和 IFN-γ。青春期运动使 VPA 处理的雄性和雌性后代在成年期抵抗焦虑和快感缺失样行为，而仅使 VPA 暴露的雄性后代在成年期抵抗行为绝望、社交和认知缺陷。运动降低了 VPA 处理的雄性后代海马体中的 IL-6、TNF-α、IFN-γ 和 IL-17，以及前额叶中的 IFN-γ 和 IL-17，而降低了 VPA 处理的雌性后代海马体中的 TNF-α 和 IFN-γ。本研究表明，青春期运动可能预防产前 VPA 暴露的后代小鼠应激相关症状、认知缺陷和神经炎症的发展。
