Inoue Takahiro, Ninuma Shuta, Hayashi Masataka, Okuda Akane, Asaka Tadayoshi, Maejima Hiroshi
a Graduate School of Health Sciences , Hokkaido University , Sapporo , Japan.
b Department of Health Sciences, School of Medicine , Hokkaido University , Sapporo , Japan.
Neurol Res. 2018 Jan;40(1):18-25. doi: 10.1080/01616412.2017.1382801. Epub 2017 Oct 11.
Objectives Brain-derived neurotrophic factor (BDNF) plays important roles in neuroplasticity in the brain. The objective of this study was to examine the effects of long-term exercise combined with low-level inhibition of GABAergic synapses on motor control and the expression of BDNF in the motor-related cortex. Methods ICR mice were divided into four groups based on the factors exercise and GABA receptor inhibition. We administered the GABA receptor antagonist bicuculline intraperitoneally (0.25 mg/kg). Mice exercised on a treadmill 5 days/week for 4 weeks. Following behavioral tests, BDNF 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. BDNF mRNA expression in the motor cortex and muscle coordination in the wire hang test decreased after administration of bicuculline, whereas bicuculline administration increased mRNA and protein expression of BDNF in the cerebellum. Discussion The present study revealed that long-term exercise increased BDNF expression in the motor cortex and facilitated a transfer of motor learning from aerobic exercise to postural coordination. Thus, aerobic exercise is meaningful for conditioning motor learning to rehabilitate patients with central nervous system (CNS) disorders. However, long-term inhibition of GABA receptors decreased the expression of cortical BDNF mRNA and decreased muscle coordination, despite the increase of BDNF in the cerebellum, suggesting that we have to consider the term of the inhibition of the GABAergic receptor for future clinical application to CNS patients.
目的 脑源性神经营养因子(BDNF)在大脑神经可塑性中发挥重要作用。本研究的目的是探讨长期运动联合低水平抑制γ-氨基丁酸能突触对运动控制及运动相关皮层中BDNF表达的影响。方法 根据运动和γ-氨基丁酸受体抑制因素将ICR小鼠分为四组。腹腔注射γ-氨基丁酸受体拮抗剂荷包牡丹碱(0.25 mg/kg)。小鼠每周5天在跑步机上运动,持续4周。行为测试后,采用逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)法检测运动皮层和小脑皮层中BDNF的表达。结果 无论是否存在荷包牡丹碱,运动均可增加运动皮层中BDNF蛋白的表达,并改善转棒试验中的运动协调性。给予荷包牡丹碱后,运动皮层中BDNF mRNA表达及悬线试验中的肌肉协调性降低,而荷包牡丹碱给药可增加小脑中BDNF的mRNA和蛋白表达。讨论 本研究表明,长期运动可增加运动皮层中BDNF的表达,并促进运动学习从有氧运动向姿势协调性的转移。因此,有氧运动对于调节运动学习以康复中枢神经系统(CNS)疾病患者具有重要意义。然而,长期抑制γ-氨基丁酸受体会降低皮层BDNF mRNA的表达并降低肌肉协调性,尽管小脑中BDNF有所增加,这表明在未来对CNS患者的临床应用中,我们必须考虑γ-氨基丁酸能受体抑制的持续时间。