Treadmill exercise ameliorates motor disturbance through inhibition of apoptosis in the cerebellum of valproic acid-induced autistic rat pups

Kim,Ji-Eun; Shin,Mal-Soon; Seo,Tae-Beom; Ji,Eun-Sang; Baek,Seong-Soo; Lee,Sam-Jun; Park,Joon-Ki; Kim,Chang-Ju

doi:10.3892/mmr.2013.1518

Treadmill exercise ameliorates motor disturbance through inhibition of apoptosis in the cerebellum of valproic acid-induced autistic rat pups

Authors:
- Ji-Eun Kim
- Mal-Soon Shin
- Tae-Beom Seo
- Eun-Sang Ji
- Seong-Soo Baek
- Sam-Jun Lee
- Joon-Ki Park
- Chang-Ju Kim
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Affiliations: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea, Department of Biochemistry, Division of Sports Science and Engineering, Korea Institute of Sports Science, Seoul 139-242, Republic of Korea, Department of Sport & Health Science, College of Natural Science, Sangmyung University, Seoul 110-743, Republic of Korea, Department of Physical Education, College of Health, Social Welfare and Education, Tong Myong University, Busan 608-711, Republic of Korea, Division of Exercise and Health Science, Incheon National University, Incheon 407-772, Republic of Korea
Published online on: June 12, 2013 https://doi.org/10.3892/mmr.2013.1518
Pages: 327-334

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Abstract

Autism is a neurological disorder that occurs during childhood and is characterized by impairments in social interaction and communication, as well as restricted and repetitive behaviors. Abnormalities of the cerebellum in autism include Purkinje cell loss and motor disturbance. In the present study, we evaluated the effect of treadmill exercise on motor coordination and balance in correlation with reelin expression and the rate of apoptosis in the cerebellum of autistic rat pups. For the induction of the autism-like animal models, 400 mg/kg valproic acid was subcutaneously injected into rat pups on postnatal day 14. Rat pups in the exercise groups were forced to run on a treadmill for 30 min, once a day, five times a week for 4 weeks, starting on postnatal day 28. Motor coordination and balance, as measured using the rotarod test and vertical pole test, were affected by the induction of autism. By contrast, treadmill exercise ameliorated motor dysfunction in the autistic rat pups. The expression levels of reelin, GAD67 and cyclin D1 in the cerebellum of the autistic rat pups were decreased, while the expression levels of these molecules were increased in autistic rat pups who engaged in treadmill exercise. In the cerebellum of the autistic rat pups, Bcl-2 expression was decreased and Bax expression was increased. By contrast, treadmill exercise enhanced Bcl-2 expression and suppressed Bax expression. The therapeutic effect of treadmill exercise on motor deficits may be due to the reelin-mediated anti-apoptotic effect on cerebellar Purkinje neurons.

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