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Matt Kelly explains how estrogen can trigger seizures by boosting excitatory glutamate activity in the brain, while progesterone and pregnenolone counteract this by enhancing inhibitory GABA receptors that calm neuronal firing.
Matt Kelly explains how estrogen can trigger seizures by boosting excitatory glutamate activity in the brain, while progesterone and pregnenolone counteract this by enhancing inhibitory GABA receptors that calm neuronal firing.
What they found was that if they injected estrogen intravenously, they could trigger a seizure. And then if they injected progesterone, they could stop the seizure. So they called an estrogenic-type seizure catamenial epilepsy. Estrogens can bind to particular receptors and make them more active, such as the glutamate class of receptors, like NMDA receptors, that are very excitatory. And also they have a component of their metabolism, not the receptor, but the downstream metabolism, that can inflammatory. So you could trigger by glutamate triggering something like a seizure. Well, it turns out that progesterone and pregnenolone, through basically a similar pathway, work on a counterpoint to the excitatory glutamate receptor class. And that counterpoint is over at the GABA, gamma-aminobutyric acid, class of receptors, which is a calming receptor. So glutamate opens up ion channels and causes an increase in neuroelectrical activity. So you could see how maybe a seizure could get triggered there. And then GABA causes a calming effect by opening, in the case of the GABA-A receptor, the chloride channels.
