Positive effects in dopaminergic nigrostriatal system by progesterone in Hemiparkinsonian model with 6-OHDA.

GAGLIO E.; YUNES R; CABRERA R.

Mar del Plata

Congreso; XLVIII Reunion Anual de la SAFE; 2016

SAFE

Parkinson?s disease is a progressive disorder that involves dopaminergic nigrostriatal neuronal death. One of the main proteins that take part in the neurodegeneration is alpha-synuclein (alpha syn). In an animal model of hemiparkinsonism with a neurotoxin 6-HODA we previously observed that progesterone subcutaneous treatment delay the appearance of motor signs. The objectives of this work were 1) to evaluate the alpha syn expression in different groups of rats, to analyze how does it work under progesterone effects and 2) evaluate possible genomic effects changes on this protein. We used adults male Sprague Dawley rats, 250 ? 300 g and 8 weeks post injured with 6-OHDA in left striatum. Rats of the different groups were evaluated by two behavioral tests: Return and Stepping to verify motor dysfunction. Rats were divided into 3 groups: 1) sham (vehicle, n:8), 2) hemiparkinsonian (HP) (6-HODA n:8) and 3) progesterone treated group ( 6-HODA + progesterone injected during 3 days, after 7 days the neurotoxin injury,(4mg/day/kg/sc/rat, n:8). Results were expressed as mean ± S.E.M and analyzed by ANOVA I or ?t? test. We observed a significant increase in alpha syn expression in the HP group. Progesterone treatment significantly decreased (p< 0.05) the expression of alpha syn compared to HP group.DNA was extracted from samples of substance nigra and corpus striatum of all groups of rats and made a sequencing analysis. Results showed no changes in the nucleotide sequence of HP groups regarding progesterone treatment group. We concluded that a possible mechanism of action in overexpression observed of alpha syn and the delay in appearance of motor signs could be associated with a non-genomic neuroprotective effect of progesterone or its metabolites.