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

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.

• Authors: Yun Xu, Wenri Zhang, Judith Klaus, Jennifer Young, Ines Koerner, Laird C Sheldahl, Patricia D Hurn, Francisco Martínez-Murillo, Nabil J Alkayed
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 39 Pg. 14489-94 (Sep 26 2006) ISSN: 0027-8424 [Print] United States
• PMID: 16971488 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• Neuroprotective Agents
• RNA, Messenger
• cocaine- and amphetamine-regulated transcript protein
• Estradiol

Topics

• Animals
• Brain Ischemia (chemically induced)
• Cells, Cultured
• Cerebral Cortex (pathology)
• Estradiol (metabolism, pharmacology)
• Female
• Infarction, Middle Cerebral Artery (chemically induced)
• Mice
• Nerve Tissue Proteins (genetics, metabolism)
• Neurons (cytology, drug effects, pathology)
• Neuroprotective Agents (metabolism, pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Up-Regulation (drug effects)