CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice

Authors

  • Shiro Sugiura,

    Corresponding author
    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
    • Division of Strokology, Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita City, Osaka, 565-0871, Japan
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  • Kazuo Kitagawa,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Emi Omura-Matsuoka,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Tsutomu Sasaki,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Shigeru Tanaka,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Yoshiki Yagita,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Kohji Matsushita,

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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  • Daniel R. Storm,

    1. Department of Pharmacology, University of Washington, Seattle
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  • Masatsugu Hori

    1. Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
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Abstract

Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser133 residue. CREB mediates expression of several neuroprotective proteins, including B-cell CLL/lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE-mediated gene transcription after ischemia is not as well studied. We investigated temporal changes in CRE-mediated gene transcription in the cerebral cortex after focal ischemia in transgenic mice with a CRE-lacZ reporter gene. In the ischemic core, X-gal-positive cells, which reflected expression of the CRE-lacZ reporter gene, were observed rarely at any time point, though transient phosphorylation of CREB was detected. In contrast, the peri-infarct area showed a persistent increase in the number of X-gal-positive cells, of which more than half were positive for neuronal nuclei (NeuN). Our results suggest that CRE-mediated gene transcription, the pattern of which is not always consistent with that of CREB phosphorylation, occurs primarily in neurons in the peri-infarct area after focal cerebral ischemia and may be a neuroprotective response against ischemic insult. © 2003 Wiley-Liss, Inc.

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