Neuroprotective effect of estradiol on the nigrostriatal dopaminergic system of male and female hemiparkinsonian rats

BURGUEÑO V.; BONACCORSO P.; CABRERA R.

Osaka

Congreso; BIT´s 10th Annual World Congress of Neurotalk 2019; 2019

BIT´s Conferences

Parkinson´s Disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra and decreased dopamine amount (DA) in the striatum (CPU). This disease is predominantly in male, so it is proposed that sex hormones, estrogen (E2) and progesterone (P4), (neuroactive steroids), have an important neuroprotective role. Our studies have focused on the action of neuroactive steroids, E2, P4, and its active metabolites, as neuroprotective and/or neurodegenerative factors. We using a model of experimental neuropathology induced by 6-OH-dopamine, which induces hemiparkinsonism in male and female rats. We also studied the possible mechanisms involved in the endogenous neuroprotection that female rats would have during the estrous cycle, proposing new therapeutic possibility against this and others neurodegenerative pathologies such as Alzheimer's disease and Lateral Amyotrophic Sclerosis. In this presentation, we focus, though in a parallel study, on male hemiparkinsonian rats treated with E2 and female rats injured in stages of the estrous cycle with high and low endogenous levels of E2. We evaluate by behavioral, neurochemical and molecular approaches, the reactivity of the nigrostriatal dopaminergic system, to treatment with E2 in male or the stage of the estrous cycle, in the female, more sensitive to this pathology. Our results allowed us to conclude that modifications in the endogenous concentrations of E2 and P4 during the estrous cycle are a highly sensitive factor for neuroprotection against neurodegenerative disease. In this effect, a series of slow (genomic) mechanisms would be involved. These would enhance neuronal survival, with the consequent adaptation of the synaptic processes, together with a rapid (non-genomic) regulation of the release and synthesis of dopamine in the dopaminergic nigrostriatal neurons. On the other hand in the injured males, treated with E2 induces a clear improvement, mainly reflected in a delay or absence of an appearance of the motor default at 8 weeks post-injury. Finally, we conclude that the treatment activates compensatory mechanisms on the synthesis and release of dopamine also as structural neuroprotection that compensates for the dopaminergic functional defect associated with this pathology.