title: Treadmill exercise ameliorates motor disturbance through inhibition of apoptosis in the cerebellum of valproic acid-induced autistic rat pups.
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.
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Mal-Soon
authors.initials: MS
authors.lastname: Shin
authors.forename: Tae-Beom
authors.initials: TB
authors.lastname: Seo
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Ji
authors.forename: Seong-Soo
authors.initials: SS
authors.lastname: Baek
authors.forename: Sam-Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Joon-Ki
authors.initials: JK
authors.lastname: Park
authors.forename: Chang-Ju
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001321:Autistic Disorder / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011597:Psychomotor Performance; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D014635:Valproic Acid / Q000009:adverse effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000091042:Reelin Protein; C000717129:Reln protein, rat; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D014635:Valproic Acid; D012697:Serine Endopeptidases; D053148:Caspase 3; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1