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Laboratory of Glial Cell Biology



The ultimate goal of the lab´s research is to investigate the bidirectional communication between neurons and microglia, the brain phagocytes, in the healthy and diseased brain. How do neurons talk to microglia? How does microglial function affect neurons? To answer these broad questions we use a multidisciplinary approach combining in vivo experiments in rodents, and human and monkey brain tissue; and in vitro experiments in primary and organotypic cultures, and human induced pluripotent stem cells (iPSCs). We use a combination of imaging and molecular biology techniques (epigenetic, transcriptomic, and metabolomic analysis) to dissect out the role of microglia during development, adult neurogenic niches, and in diseases such as epilepsy and stroke.

In the last few years, our lab has been particularly interested in the interaction between apoptosis and phagocytosis in the brain. Apoptosis, or programmed cell death, is a ubiquitous phenomenon during neurogenesis, aging and neurodegenerative diseases. An efficient phagocytosis is necessary to maintain the homeostasis of the brain parenchyma, by preventing the release of toxic intracellular compounds from the dead cell and by triggering an immunomodulatory response. In the last few years, our group has also shown that phagocytosis triggers a cascade of modulatory metabolic and transcriptional events in microglia that ultimately affect their secretome. In the adult neurogenic niche, the vast majority of apoptotic cells undergo apoptosis in the first few days of cell life and are phagocytosed by microglia (Sierra et al., Cell Stem Cell 2010), whose secretome acts as a feedback mechanism that is necessary for the long-term maintenance of the neurogenic niche (Diaz-Aparicio et al., J Neurosci 2020). In these physiological conditions, phagocytosis is extremely efficient. In contrast, it becomes rapidly and chronically impaired in mouse and human epilepsy (Abiega et al., PLoS Biol 2016), raising the idea that harnessing phagocytosis is a novel therapeutic target to accelerate the regeneration of the diseased brain (Marquez-Ropero et al., Front Immunol 2019).



Stereotaxic surgery, immunofluorescence, epifluorescent and confocal microscopy and electron microscopy, stereology-based quantification, qPCR, gene arrays, ChiPSeq, RNASeq, fluorescent-activated cell sorting, Western blot, Seahorse metabolic analysis, primary cultures, organotypic cultures, in vitro models of phagocytosis, iPSCs.


Stoelting stereotaxic surgery set up with Nanoject microcapillary injector; Leica vibratome; Heracell tissue culture incubator; Perimed Doppler cerebral blood flow analyzer.


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Latest publications

  1. Interferons: Invited guests at the brain’s gala banquet

    Márquez-Ropero, Mar; Sierra, Amanda
    Neuron (Apr, 2024) DOI: 10.1016/j.neuron.2024.03.010
  2. Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis

    Montilla, Alejandro; Zabala, Alazne; Er-Lukowiak, Marco; Rissiek, Björn; Magnus, Tim; Rodriguez-Iglesias, Noelia; Sierra, Amanda; Matute, Carlos; Domercq, María
    Cell Death & Disease (Jan, 2023) DOI: 10.1038/s41419-023-05551-3
  3. Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy

    Beccari, Sol; Sierra-Torre, Virginia; [...] Plaza-Zabala, Ainhoa; Sierra, Amanda
    Autophagy (Jan, 2023) DOI: 10.1080/15548627.2023.2165313
  4. Microglia states and nomenclature: A field at its crossroads

    Paolicelli, Rosa C.; Sierra, Amanda; [...] Wu, Long-Jun; Wyss-Coray, Tony
    Neuron (Nov, 2022) DOI: 10.1016/j.neuron.2022.10.020
  5. Susceptibility of Female Mice to the Dietary Omega-3/Omega-6 Fatty-Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia

    Rodríguez-Iglesias, Noelia; Nadjar, Agnes; Sierra, Amanda; Valero, Jorge
    International Journal of Molecular Sciences (Mar, 2022) DOI: 10.3390/ijms23063399
  6. Editorial: Assessing Microglial Function and Identity

    Sierra, Amanda; Paolicelli, Rosa Chiara
    Frontiers in Immunology (Dec, 2021) DOI: 10.3389/fimmu.2021.824866
  7. Regulation of hippocampal postnatal and adult neurogenesis by adenosine A2A receptor: interaction with brain-derived neurotrophic factor

    Ribeiro, Filipa F.; Ferreira, Filipa; Rodrigues, Rui S.; Soares, Rita; Pedro, Diogo M.; Duarte-Samartinho, Marta; Aroeira, Rita I.; Ferreiro, Elisabete; Valero, Jorge; Solá, Susana; Mira, Helena; Sebastião, Ana M.; Xapelli, Sara
    STEM CELLS (May, 2021) DOI: 10.1002/stem.3421
  8. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

    Askew, K.; Li, K.; Olmos-Alonso, A.; Garcia-Moreno, F.; Liang, Y.; Richardson, P.; Tipton, T.; Chapman, M.A.; Riecken, K.; Beccari, S.; Sierra, A.; Molnár, Z.; Cragg, M.S.; Garaschuk, O.; Perry, V.H.; Gomez-Nicola, D.
    Cell Reports (Jan, 2017) DOI: 10.1016/j.celrep.2016.12.041