Neuromodulatory Effects of Neuroactive Steroids on Physiological and Pathophysiological Conditions.

BONACCORSO P.; CABRERA R.

Macau

Conferencia; BIT´s 8th World Gene Convention; 2017

BIT´s Conference

Title: Neuromodulatory effects of Neuroactive steroids on physiological and pathophysiological conditionsDr. Ricardo Cabrera*, and Bonaccorso Marinelli María Paula *Principal Investigator, Rearch. Direction of Mendoza University and National Scientific and Technical Research Council of Argentina (CONICET) Mendoza, ArgentinaAbstractSexual steroids are related in functions that extend beyond the reproductive ones. Estrogens are involved in cognitive phenomena, synaptic plasticity, memory, neurogenesis, and neuroprotection. Since 1993 we began to develop projects trying to understand the neuromodulatory mechanisms of sex hormones on neurotransmission systems, with a special interest in the nigrostriatal dopaminergic system. Over the years, other neuromodulatory neurotransmitters systems, such as glutamatergic and GABAergic, have been incorporated and the interaction between them has been studied. With the development of the results, we began to explore the relationship between the endogenous variables of sex hormone concentration and the action of neurosteroids on animal models under physiological and pathophysiological conditions (estrus cycle, pregnancy in female rats and neurodegenerative diseases in male rats). Although some works focused only on neurochemical mechanics, these works allowed 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 amnesic effects, among others). We have shown that progesterone and allopregnanolone, the active metabolite of progesterone, modulate the activity of the nigrostriatal dopaminergic system and that this modulation is differential, depending on the dose of steroid administered in male rats or the state of the reproductive cycle of the female rat. Progesterone prevents depressive behavior in a model of Parkinson´s disease at the same time that Progesterone also exerts a neuromodulatory effect on the motor rotational behavior of male hemiparkinsonian rats while modifying the activity of the allopregnanolone synthesis enzyme, which strongly suggests a strong interaction with the GABAA receptor. All of these antecedents added to the abundant bibliography on neuroprotection and existing neuroregeneration is that it allows us to deepen day by day the potential neuroprotective effect of these steroid molecules in non-demyelinating neurodegenerative models such as Parkinson´s disease.Biography Dr. Ricardo Cabrera obtained his Ph.D. degree in Biochemistry in 1990. He is a Professor in Neurosciences and Biochemistry at the School of Health Sciences of the University of Mendoza-Argentina. He is a Senior Researcher at the same University and CONICET Argentina. Since 2016 he is the Director of research in Mendoza University (DIUM). He directs his group of researchers on neurosciences in the Institute of Biomedical Research of the University of Mendoza and CONICET. Within the two main lines of research, one studies the neuromodulatory effect of neuroactive steroids such as estrogen and progesterone on reproductive biology and another on the neuroprotective effect in Parkinson´s disease. He is a qualified researcher in Behavioral Neurosciences, Neurochemistry, Neuroendocrinology, and Neurodegenerative diseases, mainly Parkinson´s disease. During his career, he has published more than 60 scientific articles and has directed more than 15 Ph.D. doctoral theses as Director or co-director. He received an award for his scientific studies on progesterone?s neuroprotective effects on Parkinson Disease in 2011. In 2013 he earned a bronze medal award for his work on Allopregnanolone effect on the GnRH secretion from the hypothalamus of pubertal female rats. In 2014 he was incorporated to the Advisory Committee on Medical Sciences of CONICET, Argentina. Also, he became a member of the External Expert Committee in the Pharmacology Ph.D. Program in Chile.