{rfName}
Me

Indexed in

License and use

Icono OpenAccess

Citations

55

Altmetrics

Grant support

This study was supported by the following: The European Research Council (ERC) (ERC-CoG-2020-101001916); the Spanish Ministry of Economy and Competitiveness (PID2020-113007RB-I00, SAF-2017-82185-R, and RYC-2015-171899); The Alzheimer's Association (2015-NIRG-340709, AARG-17-528125, and AARG-17-528125-RAPID), The Association for Frontotemporal Degeneration (2016 Basic Science Pilot Grant Award); and the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED, Spain). Institutional grants from the Fundacion Ramon Areces and Banco de Santander to the CBMSO are also acknowledged. The salary of B. M-V. was supported by postdoctoral fellowships awarded by the Consejo Nacional de Ciencia y Tecnologia (CONACYT) of the Mexican Government (Reference CVU Number: 385084) and the Secretaria de Educacion, Ciencia Tecnologia e Innovacion (SECTEI) of the Regional Government of Ciudad de Mexico (CDMX) (SECTEI/159/2021). The salary of J.T-R was suppoerted by a FPI-UAM fellowship. The salary of E. P. M-J was supported by a Fundacion Tatiana Perez de Guzman fellowship. The salary of M. F-G was supported by a Formacion de Personal Investigador (FPI) fellowship (PRE2018-085233). The salary of M. F-G was supported by a Formacion de Personal Investigador (FPI) fellowship (PRE2021-097690).

Analysis of institutional authors

Terreros-Roncal, JuliaAuthorMárquez-Valadez BAuthorLlorens-Martín MCorresponding Author

Share

October 24, 2022
Publications
>
Review
Sí

Methods to study adult hippocampal neurogenesis in humans and across the phylogeny

Publicated to:HIPPOCAMPUS. 33 (4): 271-306 - 2023-04-01 33(4), DOI: 10.1002/hipo.23474

Authors: Terreros-Roncal, Julia; Flor-Garcia, Miguel; Moreno-Jimenez, Elena P; Rodriguez-Moreno, Carla B; Marquez-Valadez, Berenice; Gallardo-Caballero, Marta; Rabano, Alberto; Llorens-Martin, Maria

Affiliations

Center for Networked Biomedical Research on neurodegenerative diseases (CIBERNED), Madrid, Spain. - Author
CIEN Fdn, Neuropathol Dept, Madrid, Spain - Author
Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain - Author
Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, Madrid, Spain. - Author
Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CBMSO), Spanish Research Council (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain. - Author
Neuropathology Department, CIEN Foundation, Madrid, Spain. - Author
Univ Autonoma Madrid UAM, Dept Mol Neuropathol, Spanish Res Council CSIC, Ctr Biol Mol Severo Ochoa CBMSO, Madrid, Spain - Author
Univ Autonoma Madrid, Fac Sci, Dept Mol Biol, Madrid, Spain - Author
See more

Abstract

The hippocampus hosts the continuous addition of new neurons throughout life-a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single-cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long-standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high-quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.© 2022 The Authors. Hippocampus published by Wiley Periodicals LLC.

Keywords

adult hippocampal neurogenesisalzheimers-diseaseantigen retrievalautofluorescencedentate gyrushumanhuman-brainimmunohistochemistryneural progenitor cellsneuronal maturationpostmortem delayproliferating cellssingle-celltemporal-lobe epilepsyAdultAdult hippocampal neurogenesisAnimalsAntigen retrievalAutofluorescenceDoublecortin-immunopositive cellsHippocampusHumanHumansImmunohistochemistryMammalsNeural stem cellsNeurogenesisNeuronsPhylogeny

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal HIPPOCAMPUS due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position , thus managing to position itself as a Q2 (Segundo Cuartil), in the category Cognitive Neuroscience. Notably, the journal is positioned en el Cuartil Q3 for the agency WoS (JCR) in the category Neurosciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 11.01, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-04, the following number of citations:

  • WoS: 16
  • Scopus: 21
  • Europe PMC: 13

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-04:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 79.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 79 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 0.25.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/707248

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (TERREROS RONCAL, JULIA) and Last Author (LLORENS MARTIN, MARIA VICTORIA).

the author responsible for correspondence tasks has been LLORENS MARTIN, MARIA VICTORIA.