Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors
Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors
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DOI：
10.1016/j.bbrc.2020.11.032
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Soya, Hideaki
中科院分区：
文献类型：
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作者：
Koizumi, Hikaru;Hiraga, Taichi;Soya, Hideaki
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的影响。前额叶下位与谷氨酸能和多巴胺能神经元功能障碍是已知的因素，但一种减轻异常的方法仍未发现。早期丰富的环境，如啮齿动物的滚轮运动可能有助于预防，但其临床适用性非常有限。从我们的研究来看，基于乳酸门槛等生理指标的低强度运动训练（LET）很容易转化为人类，并对大脑产生积极影响。因此，青春期的LET可以改善神经发育异常，预防精神分裂症的发展。在目前的研究中，LET阻止了产前PCP治疗引起的精神分裂症动物模型对苯环利定（PCP）治疗的致敏、认知障碍和情感行为异常。此外，在产前pcp处理的小鼠中，LET增加了多巴胺的周转率，并减轻了暴露于新物体后ERK1/2的磷酸化损伤。这些结果表明，青春期LET完全改善了与pfc中谷氨酸摄取改善和多巴胺诱导的ERK1/2信号通路相关的精神分裂症样异常行为。版权所有。
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 schizophrenialike abnormal behaviors associated with improved glutamate uptake and the dopamine-induced ERK1/2 signaling pathway in the PFC. (C) 2020 Elsevier Inc. All rights reserved.