title: ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo.
abstract: The role of microglial motility in the context of adult neurodegeneration is poorly understood. In the present work, we investigated the microanatomical details of microglia-neuron interactions in an experimental mouse model of Parkinson's disease following the intraperitoneal injection of MPTP. The specific intoxication of dopaminergic neurons induces the cellular polarization of microglia, leading to the formation of body-to-body neuron-glia contacts, called gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated microglial motility in vivo blocks the activating features of microglia, such as increased cell size and number of filopodia and diminishes their phagocyting/secreting domains, as the reduction of the Golgi apparatus and the number of microglia-neuron contacts has shown. High-resolution confocal images and three-dimensional rendering demonstrate that microglia engulf entire neurons at one-to-one ratio, and the microglial cell body participates in the formation of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic degeneration in adult mammals.
authors.affiliation: Clinical and Experimental Neuroscience, School of Medicine, University of Murcia, Murcia, Spain. barcia@um.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Barcia
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Ros
authors.forename: Valentina
authors.initials: V
authors.lastname: Annese
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Carrillo-de Sauvage
authors.forename: Francisco
authors.initials: F
authors.lastname: Ros-Bernal
authors.forename: Aurora
authors.initials: A
authors.lastname: Gómez
authors.forename: José Enrique
authors.initials: JE
authors.lastname: Yuste
authors.forename: Carmen María
authors.initials: CM
authors.lastname: Campuzano
authors.forename: Vicente
authors.initials: V
authors.lastname: de Pablos
authors.forename: Emiliano
authors.initials: E
authors.lastname: Fernandez-Villalba
authors.forename: María Trinidad
authors.initials: MT
authors.lastname: Herrero
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D048429:Cell Size; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; D020764:cdc42 GTP-Binding Protein; C049347:fasudil