Estrogens modulate the expression of lysosomal proteins in a rat model of Parkinson´s disease

LEIVA N; BONNACORSO MP; MEIER G; CARVELLI L; SOSA MA; CABRERA R

Congreso; XXXVII Reunión Anual de la Sociedad de Biología de Cuyo; 2021

Sociedad de Biología de Cuyo

Parkinson´s disease (PD) is a neurodegenerative disorde characterized by the progressive loss of dopaminergic neurons from Substance Nigra Compacta. A genetic study identified 24 locis that are associated with PD, 11 of the 24 genes are involved or disrupt various functions of the autophagic-lysosomal pathways. Lysosomes participate in the degradation of macromolecules from endocytosis and autophagy processes. Epidemiological and clinical studies reveal a difference in the development of PD between genders, giving sex hormones a neuroprotective function and making them an interesting therapeutic proposal. The objective of our work is to analyze the effect of estrogens on the expression of lysosomal proteins in a rat model with the phenotype of PD. Two month old male Sprague-Dawley rats underwent stereotaxic surgery to administer 6-hydroxydopamine (6-OHDA) or artificial cerebrospinal fluid (V) to 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 (V lesion); E (V + E lesion); HP (6-OHDA lesion) and HPE (6-OHDA + E lesion). After the treatments, the animals were sacrificed and the left and right brain regions: substantia nigra and prefrontal cortex were extracted and homogenized. The samples were processed for immunoblotting using antibodies that recognizedanti- cathepsin D (CatD) and anti-actin antibodies. Preliminary results show that chronic estrogen treatment increases CatD and actin expression in the substantia nigra and the prefrontal cortex. Since the CatD protease reduces the concentration of the α-synuclein protein in PD, we inferthe present results suggest that the increase in lysosomal function would act aexerts a neuroprotective effects in cells affected by the disease. Likewise, it should be mentioned that estrogens could also modulate the organization of the cytoskeleton, as a stage of neuromodulation.