title: Mapping and kinetics of microglia/neuron cell-to-cell contacts in the 6-OHDA murine model of Parkinson's disease.
abstract: 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.
authors.affiliation: INSERM U1028; CNRS UMR5292, Lyon Neurosciences Research Center, Neuro-oncology and Neuroinflammation team, Lyon 69000, France. angevi@hotmail.fr
authors.forename: Angélique
authors.initials: A
authors.lastname: Virgone-Carlotta
authors.forename: Josselin
authors.initials: J
authors.lastname: Uhlrich
authors.forename: Muhammad Numan
authors.initials: MN
authors.lastname: Akram
authors.forename: Denis
authors.initials: D
authors.lastname: Ressnikoff
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Chantal
authors.initials: C
authors.lastname: Domenget
authors.forename: Romain
authors.initials: R
authors.lastname: Gherardi
authors.forename: Geneviève
authors.initials: G
authors.lastname: Despars
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Serge
authors.initials: S
authors.lastname: Nataf
authors.forename: Monique
authors.initials: M
authors.lastname: Touret
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001058:Apomorphine; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D004195:Disease Models, Animal; D018491:Dopamine Agonists; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology; D023062:Receptors, Interleukin-8A / Q000172:deficiency; D012399:Rotation; D013378:Substantia Nigra / Q000473:pathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018663:Adrenergic Agents; D000943:Antigens, Differentiation; D018491:Dopamine Agonists; D023062:Receptors, Interleukin-8A; C484963:Tyrobp protein, mouse; C036763:monocyte-macrophage differentiation antigen; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine
keywords: dopamine; neurodegeneration; neuroinflammation; substantia nigra