title: Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein.
abstract: We hypothesized that one of the mechanisms underlying the protection of brain injury by therapeutic hypothermia is associated with preservation of neural stem cells. We investigated effects of moderate low temperature and the contribution of a cold-inducible molecule for the stemness of neural stem cells. The MEB5 mouse neural stem cell line was cultured in the presence or absence of EGF, and apoptosis, mRNA expression, and immunocytochemistry of the differentiation markers nestin and GFAP were evaluated at 37 or 32°C. We investigated the contribution of the cold-inducible RNA binding protein (CIRP) on apoptosis and differentiation of MEB5 cells at 32°C. EGF deprivation increased the number of apoptotic cells, decreased expression of nestin, and increased expression of GFAP. The moderate low temperature prevented apoptosis and decreases in expression of GFAP in MEB5 by EGF deprivation. The moderate low temperature significantly increased expression of CIRP. siRNA against CIRP significantly increased the apoptotic cell population of MEB5 cells via EGF deprivation at 32°C. These findings suggest that moderate low temperature preserved stemness of neural stem cells and prevented cell apoptosis via the stimulation of CIRP, and one of the mechanisms of rescue of brain injury by the moderate hypothermia is associated with preservation of neural stem cells.
authors.affiliation: Division of Life Science, Advanced Research Institute of the Sciences and Humanities, Nihon University Graduate School, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Saito
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iribe
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsunemi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kazama
authors.forename: Chikako
authors.initials: C
authors.lastname: Yoshida-Noro
authors.forename: Nariyuki
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001710:Biotin / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003080:Cold Temperature; D004815:Epidermal Growth Factor / Q000172:deficiency; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D011309:Preservation, Biological; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: C106176:Cirbp protein, mouse; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D004815:Epidermal Growth Factor; D001710:Biotin; D020169:Caspases