Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus.
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.
Sasaki
Tsutomu
T
Division of Stroke Research, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. sasaki@medone.med.osaka-u.ac.jp
Kitagawa
Kazuo
K
Yagita
Yoshiki
Y
Sugiura
Shiro
S
Omura-Matsuoka
Emi
E
Tanaka
Shigeru
S
Matsushita
Kohji
K
Okano
Hideyuki
H
Tsujimoto
Yoshihide
Y
Hori
Masatsugu
M
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
D000963:Antimetabolites; D001973:Bromodeoxyuridine