TREM-1/TREM-2 Role in Reactive Astroglial Polarization to the Pro-Inflammatory Phenotype

CADENA V, ; VILLARREAL A, ; CIERI B,; RAMOS AJ

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias 2018; 2018

Reactive gliosis is a generic astroglial response to braininjury. Reactive astrocytes can further polarize into an A1pro-inflammatory-neurodegenerative phenotype. We haverecently described that TLR4/NFkB signaling facilitatesastroglial conversion to the A1 phenotype (Rosciszewskiet al., Mol. Neurobiol. 2017). Having in mind that TREM2/TREM1 and DAP12 participate in the fine-tuning of theinflammatory response by controlling TLR/NFjB signalingin immunocompetent cells, we here studied the expressionof these receptors and DAP12 intracellular adaptor in vivoafter brain ischemia and in vitro in glial cell cultures exposedto oxygen-glucose deprivation for 6 hr. Using an experimentalmodel of brain ischemia in rats, we detected TREM2 andDAP12 expression in glial cells, with a peak between 3 and 7DPI with a specific localization in the ischemic penumbra. Invitro, we observed that OGD exposure increases TREM2expression in astrocytes and microglia; reduces TREM1 inboth cell types; while DAP12 expression is not significantlyaltered by OGD. Finally, we performed co-culture experiments of ischemic explants (3 DPI) on primary glialcells. After 5 DIV, we observed that infiltrated cells fromischemic explants and mainly microglia expressed TREM2.Our results show that ischemia or OGD induces theexpression of TREM1 and TREM2 in microglia but also ina subpopulation of reactive astrocytes and the DAP12 adaptoris available to signal in these cells.This work was supported by grants PICT 2015-1451and UBACYT.