演題詳細
神経伝達物質とシグナル分子
Neurotransmitters and Signaling Molecules
| 開催日 | 2018/7/28 | |
|---|---|---|
| 時間 | 10:50 - 11:40 | |
| 会場 | Poster Venue (Hall No.1&2 Building, Kobe International Exhibition Hall) |
- 3P-001
GABA A 受容体阻害と運動は運動関連皮質におけるBDNF発現を調節する
Low-level inhibition of GABA A receptor and motor exercise modulate BDNF expression in the motor related cortex
- 井上 貴博 / Takahiro Inoue:1 新沼 柊太 / Shuta Ninuma:2 林 聖隆 / Masataka Hayashi:1 奥田 茜 / Akane Okuda:2 浅賀 忠義 / Tadayoshi Asaka:3 前島 洋 / Hiroshi Maejima:3
- 1:北海道大学大学院保健科学院 / Graduate School of Health Sciences, Hokkaido University, Sapporo, Japan 2:北海道大学医学部保健学科 / Department of Health Sciences, School of Medicine, Hokkaido University, Sapporo, Japan 3:北海道大学大学院保健科学研究院 / Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan
Objectives: Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity and neurogenesis in the central nervous system (CNS). Aerobic exercise is known to enhance BDNF expression in the brain, beneficially contributing to prevent degenerative CNS diseases. Our previous research shows that low-level inhibition of GABAA receptor increases BDNF mRNA expression in the motor cortex. Moreover, short-term exercise combined with GABAA receptor antagonist upregulates the protein abundance of BDNF in the motor cortex. However, the effects of long-term administration of GABAA receptor antagonist have not been reported. Therefore, the objective of this study was to examine the effects of long-term exercise combined with low-level GABAA receptor inhibition on the expression of BDNF in the motor cortex and cerebellum.
Methods: ICR mice were divided into 4 groups based on the two factors of exercise and GABAA receptor inhibition. We administered the GABAA receptor antagonist bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5 days a week for 4 weeks. For behavioral assessments, rotarod test and wire hang test were performed. Following the last intervention, BDNF mRNA and protein expression in the motor cortex and cerebellar cortex was assayed using RT-PCR and ELISA.
Results: Exercise increased BDNF protein in the motor cortex and improved motor coordination in the rotarod test either in the presence or absence of bicuculline. Bicuculline administration increased mRNA and protein expression of BDNF in the cerebellum, whereas bicuculline administration decreased BDNF mRNA expression in the motor cortex and downregulated muscular coordination as assessed by the wire hang test.
Discussion: The present study revealed that long-term inhibition of GABAA receptors increased the expression of BDNF mRNA and protein in the cerebellum, despite the decrease of muscle coordination and BDNF mRNA in the motor cortex, suggesting that we have to consider the term of the inhibition of GABAA receptors for future clinical application to CNS disorders. In addition, long-term exercise increased BDNF expression in the motor cortex and facilitated a transfer of motor learning from aerobic exercise to balance function in the present study. Thus, aerobic exercise is meaningful for conditioning motor learning to rehabilitate patients with CNS disorders.
研究助成：Research funds : JSPS KAKENHI Grant Number JP17H02117, JP15K12570