in brain receptors linked to seizure susceptibility and
anxiety during the menstrual cycle
A new UCLA study shows that changes in certain brain receptors
can affect seizures and anxiety during the menstrual cycle
-- findings that could lead to novel therapies for premenstrual
dysphoric disorder (PMDD, formerly known as PMS) and other
central nervous system symptoms associated with the menstrual
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 at http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn1469.pdf.
The findings also may 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
"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," said Mody, the study's lead researcher.
"If some of our findings are replicated in humans,
our study would provide some testable predictions about
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
The next step will be to determine the precise
mechanisms behind these changes, according to Mody. "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,
postdoctoral fellow; Brandon M. Stell, 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
Grants from the National Institute of Neurological
Disorders and Stroke, the Coelho Endowment, and the Training
Program in Neural Repair supported the study.
Original source: http://www.ucnewswire.org