Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

Kim,Tae-Woon; Kang,Hyun-Sik; Park,Joon-Ki; Lee,Sam-Jun; Baek,Sang-Bin; Kim,Chang-Ju

doi:10.3892/mmr.2014.2644

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

Authors:
- Tae-Woon Kim
- Hyun-Sik Kang
- Joon-Ki Park
- Sam-Jun Lee
- Sang-Bin Baek
- 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 Exercise Physiology, School of Sport Science, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea, Department of Exercise Physiology, Division of Exercise and Health Science, College of Arts and Physical Education, Incheon National University, Incheon 407-772, Republic of Korea, Department of Physical Education, College of Health, Social Welfare and Education, Tong Myong University, Busan 608-711, Republic of Korea, Department of Psychiatry, Gangneung Asan Hospital, Ulsan University, Gangneung, Gangwon 210-711, Republic of Korea
Published online on: October 15, 2014 https://doi.org/10.3892/mmr.2014.2644
Pages: 2924-2930

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Abstract

Schizophrenia is a chronic and severe mental disorder characterized by the disintegration of cognitive thought processes and emotional responses. Despite the precise cause of schizophrenia remains unclear, it is hypothesized that a dysregulation of the N‑methyl‑D‑aspartate (NMDA) receptor in the brain is a major contributing factor to its development. Brain‑derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is implicated in learning and memory processes. In the present study, we investigated in vivo the effects of voluntary wheel running on behavioral symptoms associated with NMDA receptor expression, using MK‑801‑induced schizophrenic mice. Abilify (aripiprazole), a drug used to treat human schizophrenia patients, was used as the positive control. For the assessment of behavioral symptoms affecting locomotion, social interaction and spatial working memory, the open‑field, social interaction and Morris water maze tests were conducted. For investigating the biochemical parameters, NMDA receptor expression in the hippocampal CA2‑3 regions and prefrontal cortex was detected by NMDA immunofluorescence and BDNF expression in the hippocampus was measured using western blot analysis. MK‑801 injection for 14 days induced schizophrenia‑like behavioral abnormalities with decreased expression of the NMDA receptor and BDNF in the brains of mice. The results indicated that free access to voluntary wheel running for 2 weeks alleviated schizophrenia‑like behavioral abnormalities and increased the expression of NMDA receptor and BDNF, comparable to the effects of aripiprazole treatment. In the present study, the results suggest that NMDA receptor hypofunctioning induced schizophrenia‑like behaviors, and that voluntary wheel running was effective in reducing these symptoms by increasing NMDA receptor and BDNF expression, resulting in an improvement of disease related behavioral deficits.

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