Patients with Parkinson's disease show persistent microglial activation in the areas of the brain where the degeneration of dopaminergic neurons takes place. The reason for maintaining this activated state is still unknown, but it is thought that this persistent microglial activation may contribute to the degeneration of dopaminergic neurons. In this study, we report the microanatomical details of microglia and the relationship between microglia and neurons in the substantia nigra pars compacta of Parkinsonian monkeys years after insult with MPTP. We observed that microglial cells appear polarized toward dopaminergic neurons in MPTP-treated macaques compared to untreated animals and present clear phagocytic characteristics, such as engulfing gliaptic contacts, an increase in Golgi apparatus protein machinery and ball-and-chain phagocytic buds. These results demonstrate that activated microglia maintain phagocytic characteristics years after neurotoxin insult, and phagocytosis may be a key contributor to the neurodegenerative process.
Some interesting points from the presentation:
- 'Senile microglia' are observed more during aging and they are prone to spontaneous activation. This may contribute to parkinsons disease as they are common in the elderly.
- The conventional MPTP intoxication model for PD could show only transient activation of microglia, so contribution of chronically active microglia would not be studied.
- The monkey model addresses this issue.
- The study uses advanced image processing of confocal microscopy images for analysis, which could be pursued by our department.