Project 01

Adult neurogenesis
in humans

ERC Consolidator Grant 2020, ERC-CoG-2020-101001916. “HumAN: Interrogating human adult hippocampal neurogenesis”

Further reading

Deepening our understanding on the mechanisms that drive the functional integration of new neurons in the human hippocampus is supported by the award of the ERC Consolidator Grant 2020 “HumAN: Interrogating human adult hippocampal neurogenesis” (ERC-CoG-2020-101001916).


Principal Investigator

María Llorens-Martín


HumAN is aimed at unveiling the features that confer neurogenic potential to the human hippocampus, thoroughly characterising this specialised niche in adulthood, physiological aging, and pathological conditions. By using post-mortem human brain tissue of the highest quality, bioinformatics, advanced microscopy and molecular techniques at the single-cell level, HumAN will deepen our understanding not only of the mechanisms that control the maturation and synaptic integration of newly generated cells in human beings, but also of the pathophysiology of neurodegenerative and psychiatric diseases, thereby facilitating the identification of potential therapeutic targets for these as yet incurable conditions.


Members of the team involved

María Llorens-Martín (Principal Investigator)

Alberto Rábano (Collaborator)

Berenice Márquez-Valadez

Carla Rodríguez-Moreno

Elena Moreno-Jiménez

Fabio Cafini (Collaborator)

Julia Terreros-Roncal

Marta Gallardo

Miguel Flor-García


Participating Institutions

Spanish Research Council (CSIC) (Spain) (Host Institution)

Universidad Autónoma de Madrid (UAM) (Spain)


Fundación CIEN (Spain)

Stanley Medical Research Institute (SMRI) (USA)

Results Obtained



Impact of neurodegenerative diseases on human adult hippocampal neurogenesis.

Terreros-Roncal J, Moreno-Jiménez EP, Flor-García M, Rodríguez-Moreno CB, Trinchero MF, Cafini F, Rábano A, Llorens-Martín M. (2021).

doi: 10.1126/science.abl5163.


Expand Abstract: Disrupted hippocampal performance underlies psychiatric comorbidities and cognitive impairments in patients with neurodegenerative disorders. To understand the contribution of adult hippocampal neurogenesis (AHN) to amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, dementia with Lewy bodies, and frontotemporal dementia, we studied postmortem human samples. We found that adult-born dentate granule cells showed abnormal morphological development and changes in the expression of differentiation markers.

The ratio of quiescent to proliferating hippocampal neural stem cells shifted, and the homeostasis of the neurogenic niche was altered. Aging and neurodegenerative diseases reduced the phagocytic capacity of microglia, triggered astrogliosis, and altered the microvasculature of the dentate gyrus. Thus, enhanced vulnerability of AHN to neurodegeneration might underlie hippocampal dysfunction during physiological and pathological aging in humans.


Unraveling human adult hippocampal neurogenesis.

Flor-García M, Terreros-Roncal J, Moreno-Jiménez EP, Ávila J, Rábano A, Llorens-Martín M. (2020).

Nature Protocols
doi: 10.1038/s41596-019-0267-y.


Expand Abstract: Adult neurogenesis occurs in a few selected regions of the mammalian brain. One such region is the hippocampus, the so-called gateway to memory, where adult hippocampal neurogenesis (AHN) occurs. Here, we provide a comprehensive description of the methods used in our laboratory to unambiguously detect a population of immature neurons in the human hippocampus until the 10th decade of life. The criteria used to refine and develop the current protocol include obtaining post-mortem human samples of remarkable quality and under tightly controlled conditions for immunohistochemistry (IHC) studies, optimizing tissue processing and histological procedures, establishing criteria to reliably validate antibody signal and performing unbiased stereological cell counts.

Moreover, we provide a detailed description of the parameters that, in our view, should be reported in human AHN studies. The opposing results obtained by introducing slight variations in the methodological conditions should be considered by future studies that seek to increase our knowledge of this fascinating process.

By applying simple and inexpensive tissue pre-treatments, this protocol, which can be completed in 7 days, might be applicable to a variety of IHC studies performed on other tissues of human (or animal) origin.


Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease.

Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N, Ávila J, Llorens-Martín M. (2019)

Nature Medicine
doi: 10.1038/s41591-019-0375-9. 


Expand Abstract: The hippocampus is one of the most affected areas in Alzheimer's disease (AD). Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing

methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life.

These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.


Invited talks and conferences

María Llorens-Martín

Brain Conference. 24-25 February 2022. “Human adult neurogenesis and neurodegenerative diseases”.


María Llorens-Martín

PhD Advanced Course Stem Cell Technologies. Champalimaud Foundation. 8-12 November 2021. “Human adult hippocampal neurogenesis during physiological and pathological aging”. 


María Llorens-Martín

Society for Neuroscience (SfN). 19-23 October 2019, Chicago (USA). “Human adult neurogenesis & neurodegenerative diseases”. Dual Perspectives session: ‘Does adult hippocampal neurogenesis occur in humans?’




El País

21 Oct. 2021 “Demostrada la existencia de células madre en el cerebro que permiten la generación de neuronas durante toda la vida”

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Telediario de las 21:00 - 21 Oct 2021



Centro de Biología Molecular Severo Ochoa (CBMSO) Universidad Autónoma de Madrid (Campus de Cantoblanco)
C/ Nicolás Cabrera 1 - 28049 Madrid (Spain)

María Llorens-Martín (PI)
+34 911964632