The study "Ovarian Cycle-Linked Changes in GABAA Receptors Mediating Tonic Inhibition Alter Seizure Susceptibility and Anxiety" is published in Nature Neuroscience. It is available online beginning May 15 at http://www.
The findings may also be applicable to post-partum depression and mood swings during pregnancy, and may explain how stress hormones affect the brain, said Dr. Istvan Mody, Coelho professor of neurology at the Reed Neurological Research Center at the David Geffen School of Medicine at UCLA.
"This may provide novel therapeutic targets for curing PMDD (PMS) or catamenial epilepsy, a form of epilepsy in women that is exacerbated during certain stages of the menstrual cycle, or other mental or neurological disorders related to changes in steroid hormone levels," Mody, the study's lead researcher, said. "If some of our findings are replicated in humans, our study would provide some testable predictions about new therapies."
Basing their findings on a study of the estrous cycle in mice--the equivalent of the human menstrual cycle--the researchers found that a specific subclass of the receptors called GABAA receptors change in the hippocampus during the cycle. These changes take place in a part of the brain where progesterone-derived neurosteroids are active, and are inexorably linked to an altered behavior of nerve cells, which in turn changes the whole animal's susceptibility to seizures and anxiety.
"This may be quite relevant to the way nerve cells respond to stimuli in the human brain during the menstrual cycle," Mody said.
The changes may spark seizures in women with catamenial epilepsy and may lead to the increased anxiety women experience during PMDD, according to the researchers who also filed a patent for the potential new therapies.
The next step will be to determine the precise mechanisms behind these changes, Mody said. "We have to find the molecular identities of the players responsible for changing the number of these receptors on the surface of nerve cells," he said.
Also, researchers need to learn if similar mechanisms operate in humans as well.
The other researchers were Jamie L. Maguire, Ph.D., postdoctoral fellow; Brandon M. Stell, Ph.D., a recent graduate of the UCLA Molecular, Cellular and Integrative Physiology Interdepartmental Graduate Program, and Dr. Mahsan Rafizadeh, research associate, all from the departments of neurology and physiology at the David Geffen School of Medicine at UCLA.
Grants from the National Institute of Neurological Disorders and Stroke, the Coelho Endowment and the Training Program in Neural Repair supported the study.