Laboratory of Glial Cell Biology
The ultimate goal of the lab´s research is to investigate the role of microglia cells in the healthy and diseased brain. Microglia are highly motile, and their processes constantly survey the brain parenchyma in search for alterations of the homeostasis. Traditionally microglia has been studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. We are particularly interested in the interaction between apoptosis and phagocytosis in the brain. Apoptosis, or programmed cell death, is a ubiquitous phenomenon during embryonic development, adult neurogenesis, aging and neurodegenerative diseases. While the fast and efficient removal of apoptotic debris is widely considered to be essential for the maintenance of the tissue homeostasis and brain functioning throughout life, little is known about the cellular and molecular mechanisms regulating brain phagocytosis. Recent results from the lab (Sierra et al., Cell Stem Cell 2010) have shown that the vast majority of newborn cells in adult neurogenic niches undergo apoptosis early in their lifetime and are immediately phagocytosed by resident, non-activated microglia. Microglial phagocytosis is extremely fast and efficient in these physiological conditions, challenging the established paradigm in which microglia require to be activated prior to become phagocytes. In addition to the removal of cell debris, phagocytosis may have further impact in the well being of neighboring cells, particularly in the disease brain. For instance, phagocytosis and inflammation are intimately linked, as phagocytosis of apoptotic bodies is actively anti-inflammatory. Currently, the lab investigates the functional consequences as well as the molecular mechanisms mediating the recognition, engulfment and degradation of apoptotic debris by microglia in physiological (development, adult neurogenesis) and pathological conditions.
Stereotaxic surgey, Inmunofluorescence, Epifluorescent and Confocal microscopy, Stereology-based quantification, qPCR, Western blot, Primary cultures, organotypic cultures, in vitro models of phagocytosis, fluorescent-activated cell sorting.
Stoelting stereotaxic surgery set up with Nanoject microcapillary injector; Leica vibratome; Heracell tissue culture incubator.