ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo
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...
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| Published in | Scientific reports Vol. 2; no. 1; p. 809 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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08.11.2012
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| 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. |
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| AbstractList | 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. 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. |
| ArticleNumber | 809 |
| Author | de Pablos, Vicente Barcia, Carlos Ros-Bernal, Francisco Yuste, José Enrique Fernandez-Villalba, Emiliano Gómez, Aurora Carrillo-de Sauvage, María Angeles Herrero, María Trinidad Campuzano, Carmen María Annese, Valentina Ros, Carmen María |
| Author_xml | – sequence: 1 givenname: Carlos surname: Barcia fullname: Barcia, Carlos email: barcia@um.es organization: Clinical and Experimental Neuroscience, School of Medicine, University of Murcia, Murcia, Spain. barcia@um.es – sequence: 2 givenname: Carmen María surname: Ros fullname: Ros, Carmen María – sequence: 3 givenname: Valentina surname: Annese fullname: Annese, Valentina – sequence: 4 givenname: María Angeles surname: Carrillo-de Sauvage fullname: Carrillo-de Sauvage, María Angeles – sequence: 5 givenname: Francisco surname: Ros-Bernal fullname: Ros-Bernal, Francisco – sequence: 6 givenname: Aurora surname: Gómez fullname: Gómez, Aurora – sequence: 7 givenname: José Enrique surname: Yuste fullname: Yuste, José Enrique – sequence: 8 givenname: Carmen María surname: Campuzano fullname: Campuzano, Carmen María – sequence: 9 givenname: Vicente surname: de Pablos fullname: de Pablos, Vicente – sequence: 10 givenname: Emiliano surname: Fernandez-Villalba fullname: Fernandez-Villalba, Emiliano – sequence: 11 givenname: María Trinidad surname: Herrero fullname: Herrero, María Trinidad |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23139861$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright Nature Publishing Group Nov 2012 Copyright © 2012, Macmillan Publishers Limited. All rights reserved 2012 Macmillan Publishers Limited. All rights reserved |
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| SubjectTerms | 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology 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 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 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 Rodents |
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| Title | ROCK/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo |
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