Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.

<h4>Background</h4>Essentially all knowledge about adult hippocampal neurogenesis in humans still comes from one seminal study by Eriksson et al. in 1998, although several others have provided suggestive findings. But only little information has been available in how far the situation in...

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Autores principales:	Rolf Knoth, Ilyas Singec, Margarethe Ditter, Georgios Pantazis, Philipp Capetian, Ralf P Meyer, Volker Horvat, Benedikt Volk, Gerd Kempermann
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Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e0c889b3dd54ca6a24558d239adc15e
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spelling	oai:doaj.org-article:9e0c889b3dd54ca6a24558d239adc15e2021-11-25T06:26:15ZMurine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.1932-620310.1371/journal.pone.0008809https://doaj.org/article/9e0c889b3dd54ca6a24558d239adc15e2010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20126454/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Essentially all knowledge about adult hippocampal neurogenesis in humans still comes from one seminal study by Eriksson et al. in 1998, although several others have provided suggestive findings. But only little information has been available in how far the situation in animal models would reflect the conditions in the adult and aging human brain. We therefore here mapped numerous features associated with adult neurogenesis in rodents in samples from human hippocampus across the entire lifespan. Such data would not offer proof of adult neurogenesis in humans, because it is based on the assumption that humans and rodents share marker expression patterns in adult neurogenesis. Nevertheless, together the data provide valuable information at least about the presence of markers, for which a link to adult neurogenesis might more reasonably be assumed than for others, in the adult human brain and their change with increasing age.<h4>Methods and findings</h4>In rodents, doublecortin (DCX) is transiently expressed during adult neurogenesis and within the neurogenic niche of the dentate gyrus can serve as a valuable marker. We validated DCX as marker of granule cell development in fetal human tissue and used DCX expression as seed to examine the dentate gyrus for additional neurogenesis-associated features across the lifespan. We studied 54 individuals and detected DCX expression between birth and 100 years of age. Caveats for post-mortem analyses of human tissues apply but all samples were free of signs of ischemia and activated caspase-3. Fourteen markers related to adult hippocampal neurogenesis in rodents were assessed in DCX-positive cells. Total numbers of DCX expressing cells declined exponentially with increasing age, and co-expression of DCX with the other markers decreased. This argued against a non-specific re-appearance of immature markers in specimen from old brains. Early postnatally all 14 markers were co-expressed in DCX-positive cells. Until 30 to 40 years of age, for example, an overlap of DCX with Ki67, Mcm2, Sox2, Nestin, Prox1, PSA-NCAM, Calretinin, NeuN, and others was detected, and some key markers (Nestin, Sox2, Prox1) remained co-expressed into oldest age.<h4>Conclusions</h4>Our data suggest that in the adult human hippocampus neurogenesis-associated features that have been identified in rodents show patterns, as well as qualitative and quantitative age-related changes, that are similar to the course of adult hippocampal neurogenesis in rodents. Consequently, although further validation as well as the application of independent methodology (e.g. electron microscopy and cell culture work) is desirable, our data will help to devise the framework for specific research on cellular plasticity in the aging human hippocampus.Rolf KnothIlyas SingecMargarethe DitterGeorgios PantazisPhilipp CapetianRalf P MeyerVolker HorvatBenedikt VolkGerd KempermannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8809 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rolf Knoth Ilyas Singec Margarethe Ditter Georgios Pantazis Philipp Capetian Ralf P Meyer Volker Horvat Benedikt Volk Gerd Kempermann Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
description	<h4>Background</h4>Essentially all knowledge about adult hippocampal neurogenesis in humans still comes from one seminal study by Eriksson et al. in 1998, although several others have provided suggestive findings. But only little information has been available in how far the situation in animal models would reflect the conditions in the adult and aging human brain. We therefore here mapped numerous features associated with adult neurogenesis in rodents in samples from human hippocampus across the entire lifespan. Such data would not offer proof of adult neurogenesis in humans, because it is based on the assumption that humans and rodents share marker expression patterns in adult neurogenesis. Nevertheless, together the data provide valuable information at least about the presence of markers, for which a link to adult neurogenesis might more reasonably be assumed than for others, in the adult human brain and their change with increasing age.<h4>Methods and findings</h4>In rodents, doublecortin (DCX) is transiently expressed during adult neurogenesis and within the neurogenic niche of the dentate gyrus can serve as a valuable marker. We validated DCX as marker of granule cell development in fetal human tissue and used DCX expression as seed to examine the dentate gyrus for additional neurogenesis-associated features across the lifespan. We studied 54 individuals and detected DCX expression between birth and 100 years of age. Caveats for post-mortem analyses of human tissues apply but all samples were free of signs of ischemia and activated caspase-3. Fourteen markers related to adult hippocampal neurogenesis in rodents were assessed in DCX-positive cells. Total numbers of DCX expressing cells declined exponentially with increasing age, and co-expression of DCX with the other markers decreased. This argued against a non-specific re-appearance of immature markers in specimen from old brains. Early postnatally all 14 markers were co-expressed in DCX-positive cells. Until 30 to 40 years of age, for example, an overlap of DCX with Ki67, Mcm2, Sox2, Nestin, Prox1, PSA-NCAM, Calretinin, NeuN, and others was detected, and some key markers (Nestin, Sox2, Prox1) remained co-expressed into oldest age.<h4>Conclusions</h4>Our data suggest that in the adult human hippocampus neurogenesis-associated features that have been identified in rodents show patterns, as well as qualitative and quantitative age-related changes, that are similar to the course of adult hippocampal neurogenesis in rodents. Consequently, although further validation as well as the application of independent methodology (e.g. electron microscopy and cell culture work) is desirable, our data will help to devise the framework for specific research on cellular plasticity in the aging human hippocampus.
format	article
author	Rolf Knoth Ilyas Singec Margarethe Ditter Georgios Pantazis Philipp Capetian Ralf P Meyer Volker Horvat Benedikt Volk Gerd Kempermann
author_facet	Rolf Knoth Ilyas Singec Margarethe Ditter Georgios Pantazis Philipp Capetian Ralf P Meyer Volker Horvat Benedikt Volk Gerd Kempermann
author_sort	Rolf Knoth
title	Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
title_short	Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
title_full	Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
title_fullStr	Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
title_full_unstemmed	Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
title_sort	murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/9e0c889b3dd54ca6a24558d239adc15e
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Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.

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