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Laboratory of Neurogenesis, Neuroinflammation and Network Dynamics (3ND)

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RESEARCH

Adult hippocampal neurogenesis -or generation of new functional neurons- is important for memory formation, learning, fear conditioning, anxiety and antidepressant action. Neurogenesis decreases with aging and in some neurologic disorders such as temporal lobe epilepsy. Therefore, it has been proposed that reduced neurogenesis might be involved in the appearance of particular symptoms and cognitive deficits found in those conditions.
Adult hippocampal neurogenesis occurs due to the existence of a population of neural stem cells (NSCs) in the dentate gyrus. This population, however, declines with age because their activation is coupled to their exhaustion: NSCs remain quiescent and are activated progressively to divide asymmetrically giving rise to neuronal precursors. Once they finish their round of divisions they differentiate into astrocytes losing their stem cell capabilities. This decline of NSCs and neurogenesis that occurs in a natural manner with aging might result accelerated in situations in which neuronal activity is intensely increased, such as epilepsy, as the rate of NSC activation results elevated.
Thus, in order to prevent or recover the loss of neurogenesis it is essential to comprehend the mechanisms that translate neuronal activity into NSC activation, as well as the mechanisms controlling their intrinsic properties (self-renewal, mitotic capability, differentiation…), and those of the neurogenic process (proliferation and survival of intermediate precursors, differentiation of neuroblasts…). Our goal is to understand these mechanisms and learn to manipulate them in order to fight more efficiently against the cognitive deficits associated with the loss neurogenesis.

PROGRAMME

TECHNIQUES

The core of our research is the use of transgenic mice in which neural stem and progenitors cells can be visualized due to the expression of fluorescent proteins, and confocal microscopy-based imaging. Other techniques include electron microscopy, quantitative retrotranscriptase PCR (qRT-PCR) and calcium imaging.

HIGHLIGHTED PROJECTS

  • MICINN PID2019-104766RB-C21
  • Basque Government (PIBA_2021_1_0018)
  • ApoyoDravet/INDRE

Latest publications

  1. Generation of adult hippocampal neural stem cells occurs in the early postnatal dentate gyrus and depends on cyclin D2

    Pastor-Alonso, Oier; Syeda Zahra, Anum; Kaske, Bente; García-Moreno, Fernando; Tetzlaff, Felix; Bockelmann, Enno; Grunwald, Vanessa; Martín-Suárez, Soraya; Riecken, Kristoffer; Witte, Otto Wilhelm; Encinas, Juan Manuel; Urbach, Anja
    The EMBO Journal (Dec, 2023) DOI: 10.1038/s44318-023-00011-2
  2. The differential response to neuronal hyperexcitation and neuroinflammation of the hippocampal neurogenic niche

    Ruiz-Clavijo, Lorena; Martín-Suárez, Soraya
    Frontiers in Neuroscience (Jul, 2023) DOI: 10.3389/fnins.2023.1186256
  3. Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in Drosophila

    Simões, Anabel R.; Neto, Marta; Alves, Carolina S.; Santos, Mariana B.; Fernández-Hernández, Ismael; Veiga-Fernandes, Henrique; Brea, David; Durá, Irene; Encinas, Juan M.; Rhiner, Christa
    Developmental Cell (Jul, 2022) DOI: 10.1016/j.devcel.2022.05.015
  4. Time in Neurogenesis: Conservation of the Developmental Formation of the Cerebellar Circuitry

    Rueda-Alanã, E.; Garciá-Moreno, F.
    Brain, Behavior and Evolution (Jun, 2022) DOI: 10.1159/000519068
  5. The future belongs to those who prepare for it today

    Martín-Suárez, Soraya; Encinas, Juan Manuel
    Cell Stem Cell (May, 2021) DOI: 10.1016/j.stem.2021.04.014
  6. Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome

    Martín-Suárez, Soraya; Abiega, Oihane; Ricobaraza, Ana; Hernandez-Alcoceba, Rubén; Encinas, Juan Manuel
    Frontiers in Cell and Developmental Biology (Jul, 2020) DOI: 10.3389/fcell.2020.00654
  7. Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampus

    Martín‐Suárez, Soraya; Valero, Jorge; Muro‐García, Teresa; Encinas, Juan Manuel
    Aging Cell (Aug, 2019) DOI: 10.1111/acel.12958
  8. Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain

    Schouten, M.; Bielefeld, P.; [...] Encinas, J. M.; Fitzsimons, C. P.
    Molecular Psychiatry (Jun, 2019) DOI: 10.1038/s41380-019-0440-2
  9. Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

    Luzuriaga, Jon; Pastor-Alonso, Oier; Encinas, Juan Manuel; Unda, Fernando; Ibarretxe, Gaskon; Pineda, Jose Ramon
    Frontiers in Physiology (Mar, 2019) DOI: 10.3389/fphys.2019.00347
  10. Dbx1-derived pyramidal neurons are generated locally in the developing murine neocortex

    Rueda-Alaña, Eneritz; Martínez-Garay, Isabel; Encinas, Juan Manuel; Molnar, Zoltan; García-Moreno, Fernando
    Frontiers in Neuroscience (Oct, 2018) DOI: 10.3389/fnins.2018.00792