Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, 305-8574, Ibaraki, Japan; Department of Sport Neuroscience, Advanced Research Initiative for Human High Performance (ARIHHP), Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, 305-8574, Ibaraki, Japan.
Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, 305-8574, Ibaraki, Japan.
Biochem Biophys Res Commun. 2021 Jan 1;534:610-616. doi: 10.1016/j.bbrc.2020.11.032. Epub 2020 Nov 20.
Schizophrenia is probably ascribed to perinatal neurodevelopmental deficits, and its onset might be affected by environmental factors. Hypofrontality with glutamatergic and dopaminergic neuronal dysfunction are known factors, but a way to mitigate abnormalities remains unfound. An early enriched environment such as a wheel running in rodents may contribute to the prevention, but its clinical applicability is very limited. From our studies, low-intensity exercise training (LET) based on physiological indices, such as lactate threshold, easily translates to humans and positively affects the brains. Hence, LET during adolescence may ameliorate abnormalities in neurodevelopment and prevent the development of schizophrenia. In the current study, LET prevented sensitization to phencyclidine (PCP) treatment, impairment of cognition, and affective behavioral abnormalities in an animal model of schizophrenia induced by prenatal PCP treatment. Further, LET increased dopamine turnover and attenuated the impairment of phosphorylation of ERK1/2 after exposure to a novel object in the prenatal PCP-treated mice. These results suggest that LET during adolescence completely improves schizophrenia-like abnormal behaviors associated with improved glutamate uptake and the dopamine-induced ERK1/2 signaling pathway in the PFC.
精神分裂症可能归因于围产期神经发育缺陷，其发病可能受环境因素影响。已知低额叶功能与谷氨酸能和多巴胺能神经元功能障碍有关，但减轻异常的方法仍未找到。早期丰富的环境，如啮齿动物的轮跑，可能有助于预防，但临床应用非常有限。从我们的研究中，基于生理指标（如乳酸阈值）的低强度运动训练（LET）容易转化为人类，并对大脑产生积极影响。因此，青春期的 LET 可能改善神经发育异常，预防精神分裂症的发展。在目前的研究中，LET 预防了孕鼠产前 PCPP 处理诱导的精神分裂症动物模型对苯环已哌啶（PCP）治疗的敏感性、认知障碍和情感行为异常。此外，LET 增加了多巴胺的周转率，并减轻了孕鼠暴露于新物体后 ERK1/2 磷酸化的损伤。这些结果表明，青春期的 LET 完全改善了与前额叶皮层谷氨酸摄取和多巴胺诱导的 ERK1/2 信号通路改善相关的类精神分裂症异常行为。
