Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea.
Department of Kinesiology, Art & Sports, InHa University, Incheon, Republic of Korea.
Neuropharmacology. 2018 May 1;133:451-461. doi: 10.1016/j.neuropharm.2018.02.013.
Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, HO emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer.
虽然化疗可以提高各种癌症患者的生存率，但这种治疗方法会导致急性或长期认知功能障碍，这种现象被称为化疗后认知障碍（PCCI）或“化疗脑”。运动已知对大脑功能有积极影响。因此，本研究旨在确定运动是否可以预防或缓解化疗脑引起的症状以及海马线粒体的神经可塑性和功能障碍。Wistar 大鼠被分为以下几组：对照组、对照组加运动组、化疗脑组和化疗脑加运动组。为了诱导化疗脑，将 2mg/kg 的多柔比星（DOX）——一种广泛应用于乳腺癌患者的化疗药物——溶解在生理盐水中，直接注射到腹部，每 4 周一次。运动组每周进行 6 天、每天低强度的跑步机运动，持续 4 周。使用 Morris 水迷宫和避错实验来评估认知功能，同时在海马体和齿状回评估神经可塑性和线粒体功能。化疗脑组的认知功能下降，神经发生、脑源性神经营养因子（BDNF）、原肌球蛋白相关激酶 B（TrkB）水平降低，海马体钙潴留。化疗脑组的大鼠还表现出海马体线粒体中细胞凋亡、HO 发射和通透性转换孔增加。然而，运动减轻了 DOX 治疗引起的认知功能、神经可塑性和线粒体功能障碍。因此，本研究的结果表明，低强度运动可能有助于预防各种癌症（包括乳腺癌）患者在化疗期间或之后发生认知功能障碍。
