title: Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus.
abstract: Neuronal progenitors in the adult hippocampus continually proliferate and differentiate to the neuronal lineage, and ischemic insult promotes hippocampal neurogenesis. However, newborn neurons show a progressive reduction in numbers during the initial few weeks, therefore, enhanced survival of newborn neurons seems to be essential for therapeutic strategy. Bcl-2 is a crucial regulator of programmed cell death in CNS development and in apoptotic and necrotic cell death. Therefore, we tested whether Bcl-2 overexpression enhances survival of newborn neurons in the adult mouse hippocampus under normal and ischemic conditions. Many newborn neurons in the hippocampal dentate gyrus undergo apoptosis. Human Bcl-2 expression in NSE-bcl-2 transgenic mice began at the immature neuronal stage and remained constant in surviving mature neurons. Bcl-2 significantly increased survival of newborn neurons under both conditions, but particularly after ischemia, with decreased cell death of newborn neurons in NSE-bcl-2 transgenic mice. We also clarified the effect by Bcl-2 overexpression of enhanced survival of newborn neurons in primary hippocampal cultures with BrdU labeling. These findings suggest that Bcl-2 plays a crucial role in adult hippocampal neurogenesis under normal and ischemic conditions.
authors.affiliation: Division of Stroke Research, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. sasaki@medone.med.osaka-u.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yagita
authors.forename: Shiro
authors.initials: S
authors.lastname: Sugiura
authors.forename: Emi
authors.initials: E
authors.lastname: Omura-Matsuoka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kohji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression / Q000502:physiology; D019254:Genes, bcl-2 / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D019076:Transgenes
chemical_list: D000963:Antimetabolites; D001973:Bromodeoxyuridine