Differential effects of Bcl-2 overexpression on hippocampal CA1 neurons and dentate granule cells following hypoxic ischemia in adult mice

Huai Dong Wang, Takaichi Fukuda, Tomoko Suzuki, Koichi Hashimoto, Shyh Yuh Liou, Takashi Momoi, Toshio Kosaka, Kenji Yamamoto, Hiroshi Nakanishi

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38 Citations (Scopus)

Abstract

In contrast to its known anti-apoptotic activity in sympathetic neurons, immortal neuronal cell lines, and primary cultured immature neurons of the central nervous system (CNS), the role of Bcl-2 in CNS neurons in the adult brain is poorly understood. In the present study, we examined effects of overexpression of Bcl-2 on selective neuronal death of the hippocampal CA1 neurons and the dentate granule cells induced by hypoxic ischemia in adult transgenic mice overexpressing human Bcl-2 under the control of neuron- specific enolase (NSE-hbcl-2). At the light microscopic level, numbers of TUNEL-positive cells with pyknotic nuclei were observed in the CA1 subfield of NSE-hbcl-2 transgenic mice, as well as that of wild-type mice, after hypoxic ischemic insult, although the onset of neuronal death was apparently delayed in NSE-hbcl-2 transgenic mice. The electron microscopic studies showed that morphological changes of the degenerating CA1 neurons from both groups were clearly distinct from ordinary apoptosis. In contrast, a significant amount of degenerating dentate granule cells from wild-type but not from transgenic mice had typical apoptotic nuclei by the treatment. The activation of caspase-3 was detected in the dentate granule cells but not that of the CA1 neurons. These results indicate that the overexpression of Bcl-2 effectively suppressed dentate granule cell apoptosis but only delayed cell death of the CA1 neurons induced by hypoxic ischemia, suggesting the occurrence of a non-apoptotic, caspase-3-independent mechanism for neuronal death in the CA1 subfield.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalJournal of Neuroscience Research
Volume57
Issue number1
DOIs
Publication statusPublished - Jul 1 1999

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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