Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration

Abstract

Parkinson’s disease (PD) is characterized by profound microglial driven inflammatory processes and the loss of dopamine neurons of the substantia nigra (SNc). Both microglia and dopamine neurons that are affected in the SNc are particularly vulnerable to environmental toxicants and finding more selective ways of targeting these cell types is of importance. Quantum dots (QDs) might be a useful vehicle for selectively delivering toxicants to microglia and owing to their fluorescent capability, they can be microscopically tracked within the cell. Accordingly, we assessed the impact of QDs alone and QDs conjugated to the ribosomal toxin, saporin, upon SNc microglia and dopamine neurons. We found that intra-SNc infused QDs selectively entered microglia and induced morphological changes consistent with an activated state. QDs conjugated to saporin also caused a significant loss of dopamine neurons and motor coordination (on a rotarod test) deficits, along with an increase in the inflammatory microglial actin regulatory factors, WAVE2. These data suggest that QDs might be a viable route for toxicant delivery and also has an added advantage of being fluorescently visible. Ultimately, we found SNc neurons to be exceptionally vulnerable to QD-saporin and suggest that this could be a novel targeted approach to model PD-like inflammatory pathology.