ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo

• Published in: Scientific reports 2012-11, Vol.2 (1), p.809, Article 809
• Main Authors: Barcia, Carlos, Ros, Carmen María, Annese, Valentina, Carrillo-de Sauvage, María Angeles, Ros-Bernal, Francisco, Gómez, Aurora, Yuste, José Enrique, Campuzano, Carmen María, de Pablos, Vicente, Fernandez-Villalba, Emiliano, Herrero, María Trinidad
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; 631/250/256; 631/378/1689/1718; 631/378/1934; 631/80/2373; Actin Cytoskeleton - physiology; Animals; cdc42 GTP-Binding Protein - antagonists & inhibitors; cdc42 GTP-Binding Protein - metabolism; Cdc42 protein; Cell body; Cell Size; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - physiology; Filopodia; Golgi apparatus; Golgi Apparatus - physiology; Humanities and Social Sciences; Intoxication; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Microglia - physiology; Motility; Movement disorders; MPTP; MPTP Poisoning - chemically induced; MPTP Poisoning - metabolism; MPTP Poisoning - pathology; multidisciplinary; Neurodegeneration; Neurodegenerative diseases; Neuronal-glial interactions; Neurons; Parkinson's disease; Phagocytes; Phagocytosis; Phagocytosis - drug effects; Polarization; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Rocks; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep00809

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.