PMID- 30037768 OWN - NLM STAT- MEDLINE DCOM- 20190307 LR - 20190307 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 685 DP - 2018 Oct 15 TI - Exercise and low-level GABA(A) receptor inhibition modulate locomotor activity and the expression of BDNF accompanied by changes in epigenetic regulation in the hippocampus. PG - 18-23 LID - S0304-3940(18)30478-6 [pii] LID - 10.1016/j.neulet.2018.07.009 [doi] AB - Aerobic exercise is known to increase expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and to improve cognitive function. The inhibition of GABAergic synapses enhances hippocampal plasticity as well as learning and memory. The objective of the present study was to examine the interactive effect of low-level GABA(A) receptor inhibition and exercise on behavior tests (cognitive function and locomotor activity), expression of BDNF and epigenetic regulations including the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in the hippocampus. ICR mice were divided into two groups: those who did not participate in exercise and those who participated in exercise. Each group was subdivided into two other groups: the one who received vehicle and the one who received GABA(A) receptor antagonist, bicucullin. We administered saline or bicuculline intraperitoneally to the mice at a non-epileptic dose of 0.25 mg/kg, whereas the mice were exercised on a treadmill for approximately 1 h a day, 5 days a week for 4 weeks. Novel-object recognition test and locomotor activity were assessed at a rest day approximately 4 days before the euthanasia. The mice were euthanized 4 h after the last exercise session. Aerobic exercise for 4 weeks increased mRNA and protein expression of BDNF in the hippocampus, accompanied by enhanced HAT activity. Alternatively, bicuculline administration increased HDAC activity in the hippocampus. Furthermore, exercise in the presence of bicuculline administration increased locomotor activity, indicating that exercise combined with low-level GABA(A) receptor inhibition potentiated the activity of the mice. Altogether, the present study suggested that exercise beneficially contributes to neuroprotection in the hippocampus accompanied by the up-regulation of BDNF expression and epigenetic regulation, whereas the chronic inhibition of GABA(A) receptor potentiates exercise-induced behavioral activity. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Maejima, Hiroshi AU - Maejima H AD - Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan. Electronic address: maeji@hs.hokudai.ac.jp. FAU - Ninuma, Shuta AU - Ninuma S AD - Department of Health Sciences, School of Medicine, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan. FAU - Okuda, Akane AU - Okuda A AD - Department of Health Sciences, School of Medicine, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan. FAU - Inoue, Takahiro AU - Inoue T AD - Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan. FAU - Hayashi, Masataka AU - Hayashi M AD - Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180706 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Receptors, GABA-A) RN - Y37615DVKC (Bicuculline) SB - IM MH - Animals MH - Bicuculline/*pharmacology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cognition/drug effects/physiology MH - Epigenesis, Genetic/drug effects MH - Female MH - GABA-A Receptor Antagonists/pharmacology MH - Hippocampus/*drug effects/metabolism MH - Locomotion/drug effects MH - Memory/drug effects MH - Mice MH - Mice, Inbred ICR MH - Motor Activity/drug effects MH - Physical Conditioning, Animal/*physiology MH - Receptors, GABA-A/*drug effects/metabolism OTO - NOTNLM OT - Epigenetics OT - Exercise OT - GABA OT - Neurotrophin EDAT- 2018/07/25 06:00 MHDA- 2019/03/08 06:00 CRDT- 2018/07/25 06:00 PHST- 2018/03/08 00:00 [received] PHST- 2018/06/11 00:00 [revised] PHST- 2018/07/05 00:00 [accepted] PHST- 2018/07/25 06:00 [pubmed] PHST- 2019/03/08 06:00 [medline] PHST- 2018/07/25 06:00 [entrez] AID - S0304-3940(18)30478-6 [pii] AID - 10.1016/j.neulet.2018.07.009 [doi] PST - ppublish SO - Neurosci Lett. 2018 Oct 15;685:18-23. doi: 10.1016/j.neulet.2018.07.009. Epub 2018 Jul 6.