Hypoxia/ischemia in P7 mouse brain produces TREM2 overexpression and changes in microglia/macrophages pattern

CHERTOFF, MARIELA; SHRIVASTAVA KALPANA; LLOVERA GEMMA; RECASENS MIREIA; GIMENEZ LLORT LYDIA; ACARIN LAIA

BARCELONA

Congreso; FENS FORUM 2012; 2012

FENS

Neonatal encephalopathy continues to be an important cause of death and disability in newborn infants. Microglia plays a role in inflammation and phagocytoses to repair the damage and maintain tissue homeostasis. Recent reports demonstrate that TREM2-mediated phagocytic function of microglia is required for debris clearance and CNS tissue homeostasis. 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 (P) 7 C57/BL6 mice by permanent left carotid occlusion and litters were exposure for 55 minutes in a hypoxic chamber containing 8% of oxygen at 37ºC, with controlled humidity. The age-matched controls and samples from 3 hours to 14 days after hypoxia were collected and processed for immunohistochemistry. We observed changes in the distribution pattern and morphology of microglia/macrophages (Iba-1+), not only in ischemic hemisphere (IL) but also in contralateral (CL) side as early as 3 hours post-hypoxia. The most affected regions in both hemispheres are the hippocampus and the subcortical white matter, showing maximum activated microglia after 72 hours post-hypoxia. However, morphologically activated Iba-1+ cells were observed only in the IL cortex, caudate-putamen and thalamus. Basal TREM2 expression was observed in the white matter and in the cingulum at P7 and P10. Following HI, an increase in TREM2 staining was observed in the subcortical white matter, hippocampus of both hemispheres, and in the caudate-putamen, cortex and thalamus in the IL hemisphere, following a similar expression pattern of microglia activation. In conclusion, microglia/macrophages activation and TREM2 expression is shown in areas that show neurodegeneration and atrophy. These results suggest that the down regulation of TREM2 expression and microglia activation might be involved in the progression of the tissue damage.