Hypoxia/ischemia increases the expression of TREM2 in gray and white matter of neonatal mice brain

CHERTOFF, MARIELA; SHRIVASTAVA KALPANA; GIMENEZ LLORT LYDIA

Congreso; EUROGLIA; 2013

Recently, rare variants or mutations of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) had been associated with increased risk of Alzheimer´s Disease, Frontotemporal Dementia-like Syndrome and Early onset Dementia and. The loss-of-function of TREM2 or its coreceptor DAP12 is responsible for the recessively inherited Nasu-Hakola disease (also known as PLOSL). The brains of PLOSL affected patients show strong microglial activation in the cerebral white matter. Reports demonstrate that TREM2-mediated phagocytic function of microglia is required for debris clearance and CNS tissue homeostasis. Perinatal brain injury is the underlying etiology for a host of developmental disabilities that includes spastic motor deficits and cognitive, behavioral and learning difficulties. Hence, our aim is to characterize the expression of TREM2 in the control of neuroinflammation following hypoxia/ischemia (HI) in the newborn brain. We performed HI brain damage in postnatal day 7 (P7) C57/BL6 mice by permanent left carotid occlusion and litters were exposed to 8% of oxygen balanced with nitrogen  for 50 minutes in a hypoxic chamber with controlled humidity and temperature maintained at 37ºC. Pups were then returned to their dam until sacrifice. The age-matched controls and samples from 3 hours to 7 days after hypoxia were collected and processed for immunohistochemistry. In control animals, TREM2 expression was observed in the corpus callosum and in the subventricular zone at P7 that almost disappeared at P10. Following HI, an increase in TREM2 staining was observed in the corpus callosum, hippocampus, caudate-putamen, fimbria, cortex and thalamus in the ipsilateral (IL) hemisphere, following a similar regional pattern of microglia activation. The increased expression of TREM2 was observed from 24 hours to 7 days post-hypoxia. TREM2 colocalized mainly with microglia markers, such as Iba-1 and CD68. Oligodendrocyte expression of TREM2 was also analyzed. In conclusion, HI produced an increase in TREM2 expression on the IL damaged regions. These results suggest that the modulation of TREM2 might be a possible target for damage control in neonatal brain.