Research on potential treatments for stroke and other brain injuries has recently focused on the brain’s ability to protect, heal, and repair itself after injury. Estradiol, a sex hormone, is a well-established mediator of the brain’s healing process. However, the processes by which estradiol initiates protection and repair after an injury are still under research. Recent research into a protein in the brain known as Cocaine- and Amphetamine-Regulated Transcript (CART) has shown this neuropeptide to play a role in the neuroprotective actions of estradiol. Previously, scientists believed CART was an important messenger that impacted appetite suppression, drug satisfaction, stress, and cardiovascular function. However, in a recent study, CART was found to enhance recuperation of the cerebral cortex after an ischemic stroke (1).
Ischemia is a condition characterized by insufficient blood flow, which causes a shortage of oxygen that is necessary for cellular metabolism; therefore, ischemia leads to dysfunction and death of cells including neurons. CART expression after ischemia reduced neuronal cell death and DNA damage by 37-59% (see Figure). CART-related neuroprotection was greatly increased by the presence of estradiol. Further, CART inhibition reduced the neuroprotective effects of estradiol. Therefore, CART is believed to be an important component in estradiol-mediated neuroprotection.
These results demonstrate that CART is protective against neural injury on its own and that expression of CART is greatly increased by estradiol. Therefore, stroke patients with reduced estradiol levels may experience a reduction in not only neuroprotective processes directly triggered by estradiol but downstream targets of estradiol as well. Thus, these findings impact our understanding of Hormone Replacement Therapy in stroke-injured brains as well as promote the investigation and development of therapeutic agents for treatments based on homology to CART.
- Xu, Y., Zhang, W., Klaus, J., Young, J., Koerner, I., Sheldahl, L. C., . . . Alkayed, N. J. (2006). Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection. Proceedings of the National Academy of Sciences of the United States of America, 103(39), 14489-14494.
Department of Biology
University of Mississippi