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Date of Award
College of Arts & Sciences
Both genetic and environmental factors have been linked to Parkinson’s disease (PD), a disorder resulting in the progressive loss of dopaminergic (DA) neurons in the substantia nigra. One environmental factor is 1-methyl-4-phenylpyridinium (MPP+). The exact cellular mechanisms underlying the effects of this neurotoxin are still unclear, although disruption of axonal transport is known to be triggered by MPP+. To test the hypothesis that MPP+ triggers the disruption of axonal transport, we determined its effects on the movement of particles in DA axons. Previous lab results showed that mitochondrial movement is affected by MPP+ toxicity, whereas synaptic vesicle movement is not. The goal of this work was to determine if other moving particles in axons are also affected by MPP+. The midbrains of 14-day embryonic mice, with green fluorescent protein (GFP) tagged DA neurons, were cultured in a microchamber device, which separated the axons from the cell bodies. The cultures were time-lapse imaged using confocal microscopy with or without MPP+ treatment. Mitochondria were labeled with MitoTrackerRed, whereas all other particles were assessed via transmitted light. Kymographs were created, which allowed movement and speed to be quantified. The movement of mitochondria was subtracted from the overall data to get the non-mitochondrial movement. Upon quantification, there is no significant difference in the number and speed of non-mitochondrial particles in cells that were or were not treated with MPP+. These data support the hypothesis that the effect of MPP+ on mitochondrial movement is specific. Understanding the early role that dysfunctional mitochondria may play in PD may aid in determining the pathophysiology of this disorder and may result in new treatments.
Elman, Scott, "The Parkinsonian mimetic 1-methyl-4-phenylpyridinium (MPP+) specifically decreases mitochondrial but not vesicular axonal movement in dopaminergic neurons" (2011). Undergraduate Theses—Restricted. 16.