PMID- 29287093 OWN - NLM STAT- MEDLINE DCOM- 20180207 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 12 DP - 2017 TI - Direct exposure to mild heat promotes proliferation and neuronal differentiation of neural stem/progenitor cells in vitro. PG - e0190356 LID - 10.1371/journal.pone.0190356 [doi] LID - e0190356 AB - Heat acclimation in rats is associated with enhanced neurogenesis in thermoregulatory centers of the hypothalamus. To elucidate the mechanisms for heat acclimation, we investigated the effects of direct mild heat exposure on the proliferation and differentiation of neural stem/progenitor cells (NSCs/NPCs). The NSCs/NPCs isolated from forebrain cortices of 14.5-day-old rat fetuses were propagated as neurospheres at either 37.0 degrees C (control) or 38.5 degrees C (mild heat exposure) for four days, and the effects on proliferation were investigated by MTS cell viability assay, measurement of neurosphere diameter, and counting the total number of cells. The mRNA expressions of heat shock proteins (HSPs) and brain-derived neurotrophic factor (BDNF), cAMP response element-binding (CREB) protein and Akt phosphorylation levels, and intracellular reactive oxygen species (ROS) levels were analyzed using real time PCR, Western blotting and CM-H2DCFDA assay respectively. Heat exposure under proliferation condition increased NSC/NPC viability, neurosphere diameter, and cell count. BDNF mRNA expression, CREB phosphorylation, and ROS level were also increased by heat exposure. Heat exposure increased HSP27 mRNA expression concomitant with enhanced p-Akt level. Moreover, treatment with LY294002 (a PI3K inhibitor) abolished the effects of heat exposure on NSC/NPC proliferation. Furthermore, heat exposure under differentiation conditions increased the proportion of cells positive for Tuj1 (a neuronal marker). These findings suggest that mild heat exposure increases NSC/NPC proliferation, possibly through activation of the Akt pathway, and also enhances neuronal differentiation. Direct effects of temperature on NSCs/NPCs may be one of the mechanisms involved in hypothalamic neurogenesis in heat-acclimated rats. Such heat-induced neurogenesis could also be an effective therapeutic strategy for neurodegenerative diseases. FAU - Hossain, Md Emon AU - Hossain ME AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. FAU - Matsuzaki, Kentaro AU - Matsuzaki K AUID- ORCID: 0000-0002-5942-8840 AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. FAU - Katakura, Masanori AU - Katakura M AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. AD - Department of Nutritional Physiology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan. FAU - Sugimoto, Naotoshi AU - Sugimoto N AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. AD - Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. FAU - Mamun, Abdullah Al AU - Mamun AA AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. FAU - Islam, Rafiad AU - Islam R AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. FAU - Hashimoto, Michio AU - Hashimoto M AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. FAU - Shido, Osamu AU - Shido O AD - Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171229 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chromones) RN - 0 (Heat-Shock Proteins) RN - 0 (Morpholines) RN - 0 (Reactive Oxygen Species) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - CREB-Binding Protein/metabolism MH - *Cell Differentiation MH - *Cell Proliferation/drug effects MH - Cells, Cultured MH - Chromones/pharmacology MH - Heat-Shock Proteins/metabolism MH - *Hot Temperature MH - Morpholines/pharmacology MH - Neural Stem Cells/*cytology/metabolism MH - Neurons/*cytology/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism MH - Real-Time Polymerase Chain Reaction PMC - PMC5747471 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/12/30 06:00 MHDA- 2018/02/08 06:00 PMCR- 2017/12/29 CRDT- 2017/12/30 06:00 PHST- 2017/07/16 00:00 [received] PHST- 2017/12/13 00:00 [accepted] PHST- 2017/12/30 06:00 [entrez] PHST- 2017/12/30 06:00 [pubmed] PHST- 2018/02/08 06:00 [medline] PHST- 2017/12/29 00:00 [pmc-release] AID - PONE-D-17-26463 [pii] AID - 10.1371/journal.pone.0190356 [doi] PST - epublish SO - PLoS One. 2017 Dec 29;12(12):e0190356. doi: 10.1371/journal.pone.0190356. eCollection 2017.