Mapping and kinetics of microglia/neuron cell-to-cell contacts in the 6-OHDA murine model of Parkinson's disease

• Published in: Glia Vol. 61; no. 10; pp. 1645 - 1658
• Main Authors: Virgone-Carlotta, Angélique, Uhlrich, Josselin, Akram, Muhammad Numan, Ressnikoff, Denis, Chrétien, Fabrice, Domenget, Chantal, Gherardi, Romain, Despars, Geneviève, Jurdic, Pierre, Honnorat, Jérôme, Nataf, Serge, Touret, Monique
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.10.2013; Wiley Subscription Services, Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adrenergic Agents - toxicity; Animals; Antigens, Differentiation - metabolism; Apomorphine; Cell Communication - drug effects; Cell Communication - genetics; Cell Communication - physiology; Cell Count; Disease Models, Animal; dopamine; Dopamine Agonists; Female; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Imaging, Three-Dimensional; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia - cytology; Microglia - drug effects; Microglia - physiology; Microscopy, Confocal; Neurodegeneration; neuroinflammation; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Oxidopamine - toxicity; Parkinson Disease - etiology; Parkinson Disease - genetics; Parkinson Disease - pathology; Parkinson's disease; Receptors, Interleukin-8A - deficiency; Rotation; substantia nigra; Substantia Nigra - pathology; Time Factors; Tyrosine 3-Monooxygenase - metabolism; neurodegeneration; substantia nigra; neuroinflammation; dopamine
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.22546

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