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.
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.
- MICINN PID2019-104766RB-C21
- Basque Government (PIBA_2021_1_0018)
María Moro Fernández
Generation of adult hippocampal neural stem cells occurs in the early postnatal dentate gyrus and depends on cyclin D2The EMBO Journal (Dec, 2023) DOI: 10.1038/s44318-023-00011-2
The differential response to neuronal hyperexcitation and neuroinflammation of the hippocampal neurogenic nicheFrontiers in Neuroscience (Jul, 2023) DOI: 10.3389/fnins.2023.1186256
Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in DrosophilaDevelopmental Cell (Jul, 2022) DOI: 10.1016/j.devcel.2022.05.015
Time in Neurogenesis: Conservation of the Developmental Formation of the Cerebellar CircuitryBrain, Behavior and Evolution (Jun, 2022) DOI: 10.1159/000519068
The future belongs to those who prepare for it todayCell Stem Cell (May, 2021) DOI: 10.1016/j.stem.2021.04.014
Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet SyndromeFrontiers in Cell and Developmental Biology (Jul, 2020) DOI: 10.3389/fcell.2020.00654
Phenotypical and functional heterogeneity of neural stem cells in the aged hippocampusAging Cell (Aug, 2019) DOI: 10.1111/acel.12958
Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brainMolecular Psychiatry (Jun, 2019) DOI: 10.1038/s41380-019-0440-2
Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse BrainFrontiers in Physiology (Mar, 2019) DOI: 10.3389/fphys.2019.00347
Dbx1-derived pyramidal neurons are generated locally in the developing murine neocortexFrontiers in Neuroscience (Oct, 2018) DOI: 10.3389/fnins.2018.00792