Investigating Saporin-Conjugated Quantum Dots as a Microglia Depletion Strategy in the Substantia Nigra

To study the relationship between neuroinflammation and neurodegeneration in Parkinson’s disease, we employed a relatively new biological assay using saporin-conjugated quantum dots. Conjugation of saporin, a type I ribosomal inhibitor protein, to quantum dots, which are fluorescent nanocrystals, generates a microglia-specific toxin (QD-SAP) which has been shown to selectively ablate microglia in vitro. Administration of QD-SAP in our studies shows the same microglial depletion observed in vitro, but in our in vivo studies, also shows neuronal loss. This effect in not localized to the SNc; administration of QD-SAP in the hippocampus (HPC) shows the same result. Interestingly, administration of QD-SAP in the HPC caused dopamine cell loss in the SNc. The reverse effect was not found. We suggest that it is an initial increase in inflammation, followed by a subsequent loss of homeostatic regulation upon microglial depletion, that causes neurons to die.