Hormonal fluctuations over the course of the menstrual (or estrus) cycle can have noticeable effects on the brain and behavior. During different phases of the cycle, neurons express different subtypes of the receptor for the inhibitory neurotransmitter GABA, as reported in the June issue of Nature Neuroscience, which may provide a molecular basis for some of these changes.
Up to 78% of epileptic women have more seizures during the phase when progesterone declines, a condition called catamenial epilepsy. Five percent of menstruating women have premenstrual dysphoric disorder or PMDD, and routinely experience severe anxiety and depression in the week or so before menstruation. Estrogen and progesterone affect both excitatory and inhibitory signaling in the brain, but the mechanisms behind these changes in seizure susceptibility and anxiety were unknown.
In mice, Istvan Mody and colleagues found that neurons in the hippocampus -- a brain region important in seizure generation -- expressed more of a particular subtype of inhibitory GABA receptors during the phase of the cycle when progesterone levels are low. This caused a dramatic reduction in so-called 'tonic' or persistent inhibition of neural signaling, along with corresponding increases in seizure susceptibility and anxiety. In the high-progesterone phase of the cycle, the authors found the opposite pattern: expression of this subtype of GABA receptors was higher, tonic inhibition was increased, and seizure susceptibility was reduced. Thus the authors suggest that these GABA receptor changes may be responsible for the effects of the menstrual cycle on seizure and anxiety levels seen in catamenial epilepsy and PMDD.
Istvan Mody (University of California at Los Angeles School of Medicine, CA, USA)
Additional contact for comment on paper:
Kevin Staley (University of Colorado Health Sciences Center, Denver, CO, USA)
Online publication can be accessed by clicking here.
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