CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice
Article first published online: 18 DEC 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 75, Issue 3, pages 401–407, 1 February 2004
How to Cite
Sugiura, S., Kitagawa, K., Omura-Matsuoka, E., Sasaki, T., Tanaka, S., Yagita, Y., Matsushita, K., Storm, D. R. and Hori, M. (2004), CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice. J. Neurosci. Res., 75: 401–407. doi: 10.1002/jnr.10881
- Issue published online: 20 JAN 2004
- Article first published online: 18 DEC 2003
- Manuscript Accepted: 21 OCT 2003
- Manuscript Revised: 20 OCT 2003
- Manuscript Received: 27 AUG 2003
- focal cerebral ischemia;
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.