Microglial cells are the immune cells of the brain and experts phagocytosing harmful content for parenchymal homeostasis. Apoptotic neurons generated during development, in adult neurogenic niches, and in neurodegenerative conditions leak toxic intracellular content compromising surrounding cells. Microglial phagocytosis avoids the spillover of toxic content and exerts immunomodulatory effects. However, we still do not know the molecular, metabolic and functional effects of engulfing and degrading an apoptotic cell. A global transcriptomic analysis of primary microglia exposed to apoptotic cells indicates phagocytosis-induced metabolic modulation, suggesting a positive regulation of glycolytic genes and a negative regulation of oxidative phosphorylation genes. A more in-depth analysis using Seahorse extracellular analyzer confirmed the reduction of mitochondrial metabolism and an increase in glycolytic metabolism, although not in its maximum capacity. To determine if these metabolic changes were related to mitochondrial alterations, we analyzed mitochondrial number, morphology and structure of the mitochondrial network using ultrastructural analysis coupled with confocal images. We found that phagocytosis induced a strong remodeling of the mitochondrial network, with fewer and less complex mitochondria. The correct functioning of metabolism is essential to provide energy to the cell. Thus, metabolic and mitochondrial changes could compromise cell function, as suggested by preliminary data, which indicates a reduction in the engulfing capacity of microglia 24 hours after phagocytosis. Furthermore, to study phagocytosis-induced changes in vivo, I am developing a “superphagocytosis” model using low cranial irradiation (2Gy), newborn cells of the dentate gyrus undergo apoptosis and are subsequently phagocytosed by microglia. This model offers several advantages to study phagocytosis in vivo, as it considerably increases the number of phagocytotic microglia without damaging them, or breaking the BBB. My next steps include performing single-cell RNASeq, electron microscopy and functional analysis. This data will provide us with more information about the complex process of phagocytosis, which we need to understand to use microglia as a therapeutic target in diseases where phagocytosis is impaired.