PMID- 28591153 OWN - NLM STAT- MEDLINE DCOM- 20170914 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 6 DP - 2017 TI - Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain. PG - e0177833 LID - 10.1371/journal.pone.0177833 [doi] LID - e0177833 AB - Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear's vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes. FAU - Ishikawa, Chihiro AU - Ishikawa C AD - Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. FAU - Li, Haiyan AU - Li H AD - Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. FAU - Ogura, Rin AU - Ogura R AD - Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. FAU - Yoshimura, Yuko AU - Yoshimura Y AD - Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. FAU - Kudo, Takashi AU - Kudo T AD - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan. AD - Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. FAU - Shirakawa, Masaki AU - Shirakawa M AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. AD - JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Ibaraki, Japan. FAU - Shiba, Dai AU - Shiba D AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. AD - JEM Utilization Center, Human Spaceflight Technology Directorate, JAXA, Tsukuba, Ibaraki, Japan. FAU - Takahashi, Satoru AU - Takahashi S AD - Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan. AD - Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. FAU - Morita, Hironobu AU - Morita H AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. AD - Department of Physiology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Shiga, Takashi AU - Shiga T AUID- ORCID: 0000-0002-9548-8832 AD - Laboratory of Neurobiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. AD - Mouse Epigenetics Project, ISS/Kibo experiment, Japan Aerospace Exploration Agency (JAXA), Tsukuba, Japan. AD - Department of Neurobiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. LA - eng PT - Journal Article DEP - 20170607 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptor, Serotonin, 5-HT1B) RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 112692-38-3 (Receptor, Serotonin, 5-HT1A) SB - IM MH - Animals MH - Brain/metabolism/physiology MH - Brain Mapping MH - Brain-Derived Neurotrophic Factor/*biosynthesis/metabolism MH - Gene Expression Regulation MH - Gravitation MH - Hippocampus/metabolism MH - Humans MH - Mice MH - Receptor, Serotonin, 5-HT1A/*biosynthesis/metabolism MH - Receptor, Serotonin, 5-HT1B/*biosynthesis/metabolism MH - Receptor, Serotonin, 5-HT2A/*biosynthesis/metabolism MH - Space Flight MH - Vestibule, Labyrinth/metabolism/physiology PMC - PMC5462371 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/06/08 06:00 MHDA- 2017/09/15 06:00 PMCR- 2017/06/07 CRDT- 2017/06/08 06:00 PHST- 2017/02/27 00:00 [received] PHST- 2017/05/03 00:00 [accepted] PHST- 2017/06/08 06:00 [entrez] PHST- 2017/06/08 06:00 [pubmed] PHST- 2017/09/15 06:00 [medline] PHST- 2017/06/07 00:00 [pmc-release] AID - PONE-D-17-07807 [pii] AID - 10.1371/journal.pone.0177833 [doi] PST - epublish SO - PLoS One. 2017 Jun 7;12(6):e0177833. doi: 10.1371/journal.pone.0177833. eCollection 2017.