Neuromodulatory Effects of Neuroactive Steroids on Physiological and Pathophysiological Conditions

RJ CABRERA; M P BONACCORSO MARINELLI

Otro; World Gene Convention; 2017

Sexual steroids are related in functions that extend beyond the reproductive ones. Estrogens areinvolved in cognitive phenomena, synaptic plasticity, memory, neurogenesis and neuroprotection.Since 1993 we began to develop projects trying to understand the neuromodulatory mechanismsof sex hormones on neurotransmission systems, with special interest in the nigrostriatal dopaminergicsystem. Over the years, other neuromodulatory neurotransmitters systems, such as glutamatergicand GABAergic, have been incorporated and the interaction between them has been studied. Withthe development of the results, we began to explore the relationship between the endogenous variablesof sex hormone concentration and the action of neurosteroids on animal models under physiologicaland pathophysiological conditions (estrus cycle, pregnancy in female rats and neurodegenerativesdiseases in male rats). Although some works focused only on neurochemical mechanics, these worksallowed us to postulate mechanisms of action not previously described in the literature (anxiety,inhibition of LH secretion and inhibition of copulatory behavior, memory enhancers and amnesiceffects, among others). We have shown that progesterone and allopregnanolone, active metaboliteof progesterone, modulate the activity of the nigrostriatal dopaminergic system and that thismodulation is differential, depending on the dose of steroid administered in male rats or the stateof the reproductive cycle of the female rat. Progesterone prevents depressive behavior in a modelof Parkinson´s disease at the same time that Progesterone also exerts a neuromodulatory effect onthe motor rotational behavior of male hemiparkinsonian rats, while modifying the activity of theallopregnanolone synthesis enzyme, which strongly suggests a strong interaction with the GABAAreceptor. All of these antecedents added to the abundant bibliography on neuroprotection and existingneurorregeneration, is that it allows us to deepen day by day the potential neuroprotective effectof these steroid molecules in non-demyelinating neurodegenerative models such as Parkinson´sdisease.