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Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling

dc.rights.licenseopenen_US
dc.contributor.authorABIEGA, Oihane
dc.contributor.authorBECCARI, Sol
dc.contributor.authorDIAZ-APARICIO, Irune
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorNADJAR, Agnes
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorLAYE, Sophie
ORCID: 0000-0002-3843-1012
IDREF: 11366883X
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorLEYROLLE, Quentin
dc.contributor.authorGOMEZ-NICOLA, Diego
dc.contributor.authorDOMERCQ, Maria
dc.contributor.authorPEREZ-SAMARTIN, Alberto
dc.contributor.authorSANCHEZ-ZAFRA, Victor
dc.contributor.authorPARIS, Inaki
dc.contributor.authorVALERO, Jorge
dc.contributor.authorSAVAGE, Julie C.
dc.contributor.authorHUI, Chin-Wai
dc.contributor.authorDEUDERO, Juan J.P.
dc.contributor.authorBREWSTER, Amy L.
dc.contributor.authorANDERSON, Anne E.
dc.contributor.authorZALDUMBIDE, Laura
dc.contributor.authorGALBARRIATU, Lara
dc.contributor.authorMARINAS, Ainhoa
dc.contributor.authorVIVANCO, Maria DM
dc.contributor.authorMATUTE, Carlos
dc.contributor.authorMALETIC-SAVATIC, Mirjana
dc.contributor.authorENCINAS, Juan M.
dc.contributor.authorSIERRA, Amanda
dc.date.accessioned2021-09-24T07:26:26Z
dc.date.available2021-09-24T07:26:26Z
dc.date.issued2016-05-26
dc.identifier.issn1544-9173en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112362
dc.description.abstractEnPhagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance after seizures. These results demonstrate that the efficiency of microglial phagocytosis critically affects the dynamics of apoptosis and urge to routinely assess the microglial phagocytic efficiency in neurodegenerative disorders.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectCerveau
dc.subjectSanté humaine
dc.subjectSystème nerveux central
dc.subject.enHuman health
dc.subject.enCentral nervous system
dc.title.enNeuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pbio.1002466en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed27228556en_US
bordeaux.journalPLoS Biologyen_US
bordeaux.page1-48en_US
bordeaux.volume14en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.teamPsychoneuroimmunologie et Nutrition: Approches expérimentales et cliniquesen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Biology&rft.date=2016-05-26&rft.volume=14&rft.issue=5&rft.spage=1-48&rft.epage=1-48&rft.eissn=1544-9173&rft.issn=1544-9173&rft.au=ABIEGA,%20Oihane&BECCARI,%20Sol&DIAZ-APARICIO,%20Irune&NADJAR,%20Agnes&LAYE,%20Sophie&rft.genre=article


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