Impaired mitochondrial dynamies and cell death in manganese-induced Parkinsonism.

ALAIMO A; GOROJOD RM; SIMOLA N; BEAUQUIS J; SARAVIA F; MORELLI M; KOTLER ML

Huerta Grande, Córdoba

Congreso; Congreso Anual de la Sociedad Argentina de Neurociencias (SAN); 2011

Sociedad Argentina de Neurociencias (SAN)

Mitochondria form a dynamic network by opposing actions of fusion/fission proteins. Changes in their expression or localization alter mitochondrial morphology and may promote apoptosis. Increasing evidence correlates these events with the occurrence of neurodegenerative diseases. Therefore, we focused on this topic in Manganese (Mn)-induced Parkinsonism, a disorder associated with Mn accumulation preferentially in the basal ganglia. Using MitoTracker staining we observed increased mitochondrial network fission in Mn-treated rat astrocytoma C6 cells. Moreover, Mn provoked a marked decrease on the fusión protein Opa-1 levels as well as a dramatically increase in fission protein Drp-1 levels in both cytosol and mitochondria. Mdivi-1, a newly pharmacological Drp-1 inhibitor, prevented cell death, reduced apoptotic nuclei and maintained mitochondrial network integrity. In addition, we analyzed the histological changes in rat brain sections after Mn-intrastriatal/nigral administration. Our results revealed that altered mitochondrial dynamics plays a role in Mn-induced cell death. This knowledge may provide new therapeutic tools for the treatment of Manganism and possibly other neurodegenerative diseases.