Impaired mitocondrial dynamics and cell death in manganese-induced Parkinsonism

AGUSTINA ALAIMO; GOROJOD R. M.; SIMOLA N; BEAUQUIS J; SARAVIA F; MORELLI M; KOTLER M.L

Ciudad Autonoma de Buenos Aires

Workshop; Workshop Fronteras en Biociencias. Simposio Conjunto de la Sociedad Max Planck y el Ministerio de Ciencia, Tecnología e Innovación Productiva Polo Científico; 2012

Simposio Conjunto de la Sociedad Max Planck y el Ministerio de Ciencia, Tecnología e Innovación Productiva Polo Científico

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  fusion 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.