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 Alkayed

Research output: Contribution to journalArticle

94 Citations (Scopus)

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

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Amphetamine
Cocaine
Estradiol
Brain Injuries
Estrogens
Neurons
Cyclic AMP Response Element-Binding Protein
Brain
Response Elements
Oligonucleotide Array Sequence Analysis
Brain Ischemia
Neurodegenerative Diseases
Cerebral Cortex
Up-Regulation
Stroke
Neuroprotection
Messenger RNA
Peptides
Wounds and Injuries

Keywords

  • Estrogen
  • Ischemia
  • Stroke

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection. / Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 39, 26.09.2006, p. 14489-14494.

Research output: Contribution to journalArticle

Xu, Yun ; Zhang, Wenri ; Klaus, Judith ; Young, Jennifer ; Koerner, Ines ; Sheldahl, Laird C. ; Hurn, Patricia D. ; Martínez-Murillo, Francisco ; Alkayed, Nabil. / Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 39. pp. 14489-14494.
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