Serge Nataf and Monique Touret equally contributed to this work.
Mapping and kinetics of microglia/neuron cell-to-cell contacts in the 6-OHDA murine model of Parkinson's disease
Version of Record online: 25 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 61, Issue 10, pages 1645–1658, October 2013
How to Cite
Virgone-Carlotta, A., Uhlrich, J., Akram, M. N., Ressnikoff, D., Chrétien, F., Domenget, C., Gherardi, R., Despars, G., Jurdic, P., Honnorat, J., Nataf, S. and Touret, M. (2013), Mapping and kinetics of microglia/neuron cell-to-cell contacts in the 6-OHDA murine model of Parkinson's disease. Glia, 61: 1645–1658. doi: 10.1002/glia.22546
- Issue online: 24 AUG 2013
- Version of Record online: 25 JUL 2013
- Manuscript Accepted: 28 MAY 2013
- Manuscript Revised: 23 MAY 2013
- Manuscript Received: 28 FEB 2013
- AFP (French Parkinson Research Society) (to S. N.)
- substantia nigra
As neuroinflammatory processes are involved in the pathogenesis of Parkinson's disease (PD), we provide several key data describing the time-course of microglial accumulation in relation with behavioral alterations and neurodegeneration in a murine model of PD induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). Our study argues for a major role of microglia which accumulation is somehow early and transient in spite of the neuronal loss progression. Moreover, we observed less 6-OHDA-induced neurodegeneration associated with less inflammatory reaction in DAP-12 Knock-In mice. The direct cell-to-cell contacts that may support physical interactions between microglia and altered dopaminergic neurons are ill-defined, while it is currently hypothesized that microglia support an immune-mediated amplification of neurodegeneration by establishing a molecular cross talk with neurons. Indeed, we sought to map microglia/neuron appositions in substantia nigra (SN) of 6-OHDA injected C57Bl/6 mice and CX3CR1/GFP/+ mice. Confocal immunofluorescence analyses followed by 3D reconstitutions reveal close appositions between the soma of TH+ neurons and microglial cell bodies and ramifications. Interestingly, some microglial ramifications penetrated TH+ somas and about 40% of GFP+ microglial cells in the injured SN harbored TH+ intracytoplasmic inclusions. These results suggest a direct cross talk between neurons and microglia that may exert a microphagocytic activity toward TH+ neurons. Altogether, these results obtained in a murine PD model may participate in the understanding of microglial cells' function in neurodegenerative diseases. GLIA 2013;61:1645–1658