Abstract
Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood and brain concentration of neuroactive steroids strongly contribute to GABAA receptor function and plasticity. In this review, we listed several interesting results regarding the regulation and plasticity of GABAA receptor function during pregnancy and postpartum period in rats. The increase in brain levels of neuroactive steroids during pregnancy and their sudden decrease immediately before delivery are causally related to changes in the expression/function of specific GABAA receptor subunits in the hippocampus. These data suggest that alterations in GABAA receptor expression and function may be related to neurological and psychiatric disorders associated with crucial periods in women. These findings could help to provide potential new treatments for these women's disabling syndromes.
Highlights
Pregnancy and postpartum period are crucial periods for a woman’s life where many physiological changes take place, especially at the hormone levels
Α and β subunits are currently present in all different receptor compositions; the γ subunit is mainly associated with GABAA receptor (GABAAR) expressed in the synaptic compartment, while δ is associated with receptors present at extrasynaptic level [2,3,4]
As mentioned in the previous section, in addition to synaptic GABAARs, which are responsible for phasic inhibition, granule cells of the dentate gyrus in adult rats express a high concentration of extrasynaptic receptors that are formed mainly by the combination of α4, βn, and δ subunits [39], which are the first candidate for the tonic conductance of GABAergic inhibition in this cell population
Summary
Pregnancy and postpartum period are crucial periods for a woman’s life where many physiological changes take place, especially at the hormone levels. Several neurotransmitter systems, such as the GABAergic system, are subject to such hormonal fluctuations, undergoing, in response, dramatic functional changes. Several research groups have directed their studies on the effects of neuroactive steroid fluctuations during fundamental time window in female rodents such as menstrual cycle, pregnancy, and postpartum period and the consequent changes in blood and brain concentrations of neuroactive steroids that can strongly affect the expression and function of specific GABAAR subunits [20]. We summarize a series of findings that emerged from our and other research groups related to the differential changes in the expression and function of both synaptic and extrasynaptic GABAARs in the rat hippocampus during pregnancy and after delivery
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