THE NEUROPROTECTIVE ROLE OF ESTROGEN IN A RATS MODEL OF PARKINSON'S DISEASE.

MEIER GEORGINA; BONACCORSO MP; CARVELLI LORENA; SOSA MA; CABRERA RICARDO; LEIVA NATALIA

Ciudad de Mendoza

Congreso; XL Reunión Anual de la Sociedad de Biología de Cuyo; 2022

SOCIEDAD DE BIOLOGÍA DE CUYO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra compacta and an intracellular accumulation of the protein α-synuclein, a cytosolic and presynaptic protein. A genetic study identified twenty-four loci associated with PD, one of which was related to autophagic-lysosomal pathways. Lysosomes participate in the degradation of macromolecules from endocytic processes. Epidemiological andclinical studies reveal a difference in the development of PD between genders, giving sex hormones a neuroprotective function and turning them into an interesting therapeutic proposal. The objective of this study was to determine the effect of estrogens on the expression of lysosomal proteins in rats with the PD phenotype. Two-month-old male SpragueDawley rats underwent stereotaxic surgery to deliver 6-hydroxydopamine (6-OHDA) or artificial cerebrospinal fluid (V) into the left striatum. After 7 days, they received chronic treatment for 10 days with 17-β-Estradiol (E) or V. The groups were made up of C (lesion V); E (lesion V + E); HP (6-OHDA lesion) and HPE (6-OHDA + E lesion). After the treatments, the animals were sacrificed and the left and right brain regions were extracted: substantia nigra, prefrontal cortex and striatum. Samples were processed for immunoblotting using anti-cathepsin D (CatD) and anti-actin. Preliminary results show that chronic estrogen treatment in parkinsonian rats increases lysosomal enzyme CatD and actin expression in the substantia nigra, prefrontal cortex, and left striatum. Since CatD reduces the concentration of αsynuclein protein in PD, our results suggest that in animals with PD, estrogen exerts a neuroprotective effect through an increase in its lysosomal function. In turn, estrogens could also modulate the organization of the cytoskeleton, as a neuromodulation stage in these brain regions.