What are neurosteroids and why are they important?
The brain has excitatory (meaning an action is likely to happen) and inhibitory (meaning an action is less likely to happen) mechanisms. Seizures can be caused by a deficiency in inhibition or an increase in excitation. A neurotransmitter known as gamma amino butyric acid (GABA) and its receptors (GABARs) are critical for inhibition.
GABARs are located on the membrane of neurons and are made up of subunits that are arranged in a unique way. GABARs cause inhibition by allowing chloride (Cl-) ions to pass through the membrane. Interestingly, subunit composition of GABARs has been shown to change with a woman’s cycle.
Neurosteroids are compounds that can alter excitability of neurons or brain cells in a very rapid manner. As mentioned, an important neurosteroid is allopregnanolone (which is derived from progesterone). Scientists have been investigating its effects on seizures. Neurosteroids are capable of directly activating GABARs; hence they produce an immediate effect on neuronal excitability.
How are neurosteroid levels in the body related to the frequency of seizures?
One possible mechanism underlying catamenial epilepsy is a change in levels of neurosteroids. Another mechanism is a modification in GABARs.
It has been noticed that a sudden decrease in progesterone and neurosteroids leads to increased excitability. Therefore, it could be that withdrawal of progresterone and neurosteroids during certain phases of the menstrual cycle may lead to increased seizures. Indeed, this observation has led to a model of catamenial epilepsy in rodents known as the "neurosteroid withdrawal" method.