Estrogen Receptor Beta Identified as Potential Drug Target for Emotional Disorders

In the latest publication from CNRCS, researchers describe the effects of a novel estrogen receptor beta (ERβ) ligand on neurons that regulate emotion. Their findings are featured in the January 31 issue of Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The data reported in this paper reveals that ERβ is involved in the regulation of mood and depression. The team found that exposure to this experimental ligand caused a shift in the balance between excitatory and inhibitory neurotransmission in favor of inhibition, due in part to increased synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

The central nervous system operates by relaying electrical signals to and from nerve cells via neurons. Throughout the nervous system, nerve cells either receive signals via dendrites or send signals via axons. Signals received by dendrites are first detected by protrusions known as dendritic spines, which the CNRCS team found to be reduced in number in animals treated with the ERβ ligand.

Within the brain, GABA functions as an inhibitor by calming neuronal excitability and balancing mood. This is achieved by actively transmitting signals that inhibit, or slow, the activity of neurons. GABA is recognized as the primary inhibitory neurotransmitter. GABA receptors are targets of many sedatives within the pharmaceutical industry.

“ERβ plays an important role in the central nervous system and brain diseases through the regulation of the plasticity of dendritic spines and synapses,” explains Dr. Jan-Åke Gustafsson, director of CNRCS. “Our findings indicate the potential for treatment of neurological diseases through drugs that bind selectively to ERβ.”

The study was supported by grants from the Robert A. Welch Foundation, Eli Lilly, the Swedish Cancer Fund and the Texas Emerging Technology Fund.

Established in 1914, PNAS is among most-cited multidisciplinary scientific research journals and reports on the progressive research of the Academy. The circulation reaches over 3,000 institutions in more than 60 countries, including more than 2,200 Academy members and more than 400 foreign associates.

Established in 2009, CNRCS is the focal point of the UH health initiative. Led by Gustafsson, a world-renowned expert in the field of nuclear receptors, CNRCS researchers are involved in many aspects of nuclear receptor research, all focused on understanding the roles of these receptors in health and disease. CNRCS researchers are working toward the goal of finding new treatments for an array of significant diseases including cancer, diabetes and metabolic syndrome and degenerative neurologic diseases. Working from the Center's world-class labs, CNRCS researchers combine interdisciplinary research and dynamic collaboration with the Texas Medical Center and industry partners.

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