Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus

Tsutomu Sasaki, Kazuo Kitagawa, Yoshiki Yagita, Shiro Sugiura, Emi Omura-Matsuoka, Shigeru Tanaka, Kohji Matsushita, Hideyuki Okano, Yoshihide Tsujitnoto, Masatsugu Hori

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62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalJournal of neuroscience research
Volume84
Issue number6
DOIs
Publication statusPublished - 2006 Nov 1

Keywords

  • Bcl-2
  • Hippocampus
  • Ischemia
  • Neurogenesis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Sasaki, T., Kitagawa, K., Yagita, Y., Sugiura, S., Omura-Matsuoka, E., Tanaka, S., Matsushita, K., Okano, H., Tsujitnoto, Y., & Hori, M. (2006). Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus. Journal of neuroscience research, 84(6), 1187-1196. https://doi.org/10.1002/jnr.21036