Exercise combined with low-level GABAA receptor inhibition up-regulates the expression of neurotrophins in the motor cortex

Abstract

Neurotrophins play a crucial role in neuroplasticity, neurogenesis, and neuroprotection in the central nervous system. Aerobic exercise is known to increase the expression of BDNF in the cerebral cortex. Several animal studies have evaluated the tonic inhibition of GABAergic synapses to enhance hippocampal plasticity as well as learning and memory, whereas the effects of GABAergic inhibition on plasticity in the cerebral cortex related to motor learning are not well characterized. The objective of the present study was to examine the interactive effect of low-level GABA_A receptor inhibition and exercise on the expression of neurotrophins including BDNF in the murine motor cortex. ICR mice were randomly distributed among 4 groups based on two factors of GABA_A receptor inhibition and exercise, i.e. control group, an exercise group, a bicuculline group, and an exercise plus bicuculline group. We administered GABA_A receptor antagonist, bicuculline intraperitoneally to the mice (bicuculline and exercise plus bicuculline group) at a non-epileptic dose of 0.25mg/kg, whereas the mice (exercise and exercise plus bicuculline group) were exercised on a treadmill for 1h every day. After two week intervention, the expression of mRNA and protein abundance of neurotrophins in the motor cortex was assayed using Real time PCR and ELISA. BDNF gene expression was significantly increased by approximately 3-fold in the bicuculline group relative to the control, exercise, and bicuculline plus exercise groups. Protein abundance of BDNF expression was significantly increased by approximately 3-fold in the bicuculline plus exercise group relative to other groups. Therefore, the present study revealed that combined GABA_A receptor inhibition and moderate aerobic exercise up-regulated BDNF protein expression in the motor cortex without producing side effects on motor or cognitive functions. Alterations in BDNF expression could positively contribute to plasticity by regulating the balance between EPSPs and IPSPs in the motor cortex and thus providing a more appropriate neuronal condition for motor learning and recovery.

Keywords: Exercise; GABA; Motor cortex; Neurotrophin.