Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec 10;12(1):108.
doi: 10.1186/s13041-019-0522-8.

Expression of progenitor cell/immature neuron markers does not present definitive evidence for adult neurogenesis

Hideo Hagihara  1 , Tomoyuki Murano  1 , Koji Ohira  1   2 , Miki Miwa  3 , Katsuki Nakamura  3 , Tsuyoshi Miyakawa  4
Affiliations
Review

Expression of progenitor cell/immature neuron markers does not present definitive evidence for adult neurogenesis

Hideo Hagihara et al. Mol Brain. .

Abstract

It is agreed upon that adult hippocampal neurogenesis (AHN) occurs in the dentate gyrus (DG) in rodents. However, the existence of AHN in humans, particularly in elderly individuals, remains to be determined. Recently, several studies reported that neural progenitor cells, neuroblasts, and immature neurons were detected in the hippocampus of elderly humans, based on the expressions of putative markers for these cells, claiming that this provides evidence of the persistence of AHN in humans. Herein, we briefly overview the phenomenon that we call "dematuration," in which mature neurons dedifferentiate to a pseudo-immature status and re-express the molecular markers of neural progenitor cells and immature neurons. Various conditions can easily induce dematuration, such as inflammation and hyper-excitation of neurons, and therefore, the markers for neural progenitor cells and immature neurons may not necessarily serve as markers for AHN. Thus, the aforementioned studies have not presented definitive evidence for the persistence of hippocampal neurogenesis throughout adult life in humans, and we would like to emphasize that those markers should be used cautiously when presented as evidence for AHN. Increasing AHN has been considered as a therapeutic target for Alzheimer's disease (AD); however, given that immature neuronal markers can be re-expressed in mature adult neurons, independent of AHN, in various disease conditions including AD, strategies to increase the expression of these markers in the DG may be ineffective or may worsen the symptoms of such diseases.

Keywords: Adult neurogenesis; Dematuration; Dentate gyrus; Granule cells; Hippocampus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Immature neuronal markers expressed during dematuration and neurogenesis. Dematuration of mature neurons can be induced by several factors, such as neural hyper-excitation and inflammation. Consequently, immature neuronal markers can be re-expressed in pre-existing mature neurons, independent of adult neurogenesis. GCL, granule cell layer. SGZ, subgranular zone
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, Rábano A, Cafini F, Pallas-Bazarra N, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25:554–560. doi: 10.1038/s41591-019-0375-9. - DOI - PubMed
    1. Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, et al. Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell. 2018;22:589–599. doi: 10.1016/j.stem.2018.03.015. - DOI - PMC - PubMed
    1. Tobin MK, Musaraca K, Disouky A, Shetti A, Bheri A, Honer WG, et al. Human hippocampal neurogenesis persists in aged adults and Alzheimer’s disease patients. Cell Stem Cell. 2019;24:974–982. doi: 10.1016/j.stem.2019.05.003. - DOI - PMC - PubMed
    1. Herrup K, Yang Y. Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci. 2007;8:368–378. doi: 10.1038/nrn2124. - DOI - PubMed
    1. Sharma R, Kumar D, Jha NK, Jha SK, Ambasta RK, Kumar P. Re-expression of cell cycle markers in aged neurons and muscles: whether cells should divide or die? Biochim Biophys Acta Mol basis Dis. 1863;2017:324–336. - PubMed

Publication types