Rotenone induces regionally distinct α-synuclein protein aggregation and activation of glia prior to loss of dopaminergic neurons in C57Bl/6 mice
Savannah M. Rocha, Collin M. Bantle, Tawfik Aboellail, Debotri Chatterjee, Richard J. Smeyne, Ronald B. Tjalkens
Abstract
DAn in the SNpc. The majority of neuronal loss in the SNpc occurred during the two-week period after rotenone exposure, subsequent to the peak of microglia and astrocyte activation, as well as the peak of p129 aggregation. A secondary peak of p129 coincided with neurodegeneration at later timepoints. These data indicate that systemic exposure to rotenone in C57Bl/6 mice causes progressive accumulation and regional spread of p129 aggregates that precede maximal loss of DAn. Thus, activation of glial cells and aggregation of p129 appear to drive neuronal loss following neurotoxic stress imposed by exposure to rotenone.
Topics & Concepts
Substantia nigraRotenonePars compactaNeurodegenerationNeuroinflammationMicrogliaDopaminergicAstrogliosisDopamineNeurochemicalChemistryCell biologyAstrocyteNeuroscienceBiologyInternal medicineMitochondrionImmunologyCentral nervous systemMedicineInflammationDiseaseParkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsBiochemical and biochemical processes