Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

Yun Xu, Wenri Zhang, Judith Klaus, Jennifer Young, Ines Koerner, Laird C. Sheldahl, Patricia D. Hurn, Francisco Martínez-Murillo, Nabil J. Alkayed

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)14489-14494
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number39
DOIs
StatePublished - Sep 26 2006

Keywords

  • Estrogen
  • Ischemia
  • Stroke

ASJC Scopus subject areas

  • General

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