|
|
|
|
Neuronal Hyperactivity Disturbs ATP Microgradients,Impairs Microglial Motility,and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling
|
|
|
|
|
|
|
|
نویسنده
|
abiega o. ,beccari s. ,diaz-aparicio i. ,nadjar a. ,layé s. ,leyrolle q. ,gómez-nicola d. ,domercq m. ,pérez-samartín a. ,sánchez-zafra v. ,paris i. ,valero j. ,savage j.c. ,hui c.-w. ,tremblay m.-è. ,deudero j.j.p. ,brewster a.l. ,anderson a.e. ,zaldumbide l. ,galbarriatu l. ,marinas a. ,vivanco m.d. ,matute c. ,maletic-savatic m. ,encinas j.m. ,sierra a.
|
|
منبع
|
plos biology - 2016 - دوره : 14 - شماره : 5
|
|
چکیده
|
Phagocytosis 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. © 2016 abiega et al.
|
|
|
|
|
آدرس
|
achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, université bordeaux segalen,bordeaux, France, université bordeaux segalen,bordeaux, France, université bordeaux segalen,bordeaux, France, centre for biological sciences,university of southampton,southampton, United Kingdom, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa,spain,ikerbasque foundation,bilbao, Spain, centre de recherche du chu de québec,axe neurosciencesqc,canada,université laval,département de médecine moléculaireqc, Canada, centre de recherche du chu de québec,axe neurosciencesqc,canada,université laval,département de médecine moléculaireqc, Canada, centre de recherche du chu de québec,axe neurosciencesqc,canada,université laval,département de médecine moléculaireqc, Canada, baylor college of medicine,the jan and dan duncan neurological research institute at texas children’s hospital,houston,tx, United States, baylor college of medicine,the jan and dan duncan neurological research institute at texas children’s hospital,houston,tx, United States, baylor college of medicine,the jan and dan duncan neurological research institute at texas children’s hospital,houston,tx, United States, university hospital of cruces,bilbao, Spain, university hospital of cruces,bilbao, Spain, university hospital of cruces,bilbao, Spain, cic biogune,derio, Spain, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa, Spain, centre de recherche du chu de québec,axe neurosciencesqc, Canada, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa,spain,baylor college of medicine,the jan and dan duncan neurological research institute at texas children’s hospital,houston,tx, United States, achucarro basque center for neuroscience,bizkaia science and technology park,zamudio,spain,university of the basque country,leioa,spain,baylor college of medicine,the jan and dan duncan neurological research institute at texas children’s hospital,houston,tx, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|