Pesticides, toxic aldehydes and parkinsonism

ROMINA DEZA-PONZIO ; PAULA A. ALBRECHT; MIRIAM B. VIRGOLINI; LUCÍA FERNANDEZ HUBEID; LILIANA M. CANCELA

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Neurociencia

The catecholaldehyde hypothesis for the pathogenesis of Parkinson´s disease (PD) confers a main role to toxic aldehyde accumulation, including 4H-NE (4-hydroxynonenal) and the dopamine (DA) metabolite DOPAL (3,4-dihydroxiphenylacetaldehyde). DOPAL levels are not only determined by ALDH (aldehyde dehydrogenase) activity, but also by the adequate functionality of VMAT (vesicular monoamine transporter) and the DA cytosolic transporter DAT. Interestingly, ALDH is inhibited directly by benomyl and indirectly by rotenone. On this basis, we propose that the exposure to these pesticides in the model organism Caernorhabditis elegans would induce DOPAL accumulation as result of ALDH inhibition, a condition that would be potentiated by the interference in VMAT functionality, leading to the organism to develop a PD-like phenotype in a pro-oxidant environment. Thus, this project is a confluence of state-of-the-art tools to induce genetically-modified C. elegans strains exposed to rotenone or benomyl with behavioral tests (locomotor activity), semi-quantitative (DAergic neurons and ALDH fluorescence) and quantitative assays (LD50 for rotenone and benomyl, DA and metabolite levels, 4H-NE levels, mitochondrial complex I activity, and O2 consumption). Furthermore, the use of C. elegans strains exhibiting VMAT inactivation will potentiate DOPAL accumulation in the nigro striatal terminal of the pesticide-exposed animals, providing further evidences to the environmental basis of PD etiology.