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Tracking cell turno...
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Roeder, Sebastian S.Dresden University of Technology,University Hospital Erlangen
(författare)
Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:32d4f2e5-4991-48ba-9a1e-0ce06121ccaa
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https://lup.lub.lu.se/record/32d4f2e5-4991-48ba-9a1e-0ce06121ccaaURI
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https://doi.org/10.3389/fnins.2023.1274607DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:154068892URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15N-thymidine. Detection of 15N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo15N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Bonnin, Elisa A.University Medical Center Göttingen
(författare)
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Wu, Ting DiCurie Institute, Paris
(författare)
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Guerquin-Kern, Jean LucCurie Institute, Paris
(författare)
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Jabari, SamirFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Brandner, SebastianFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Eyüpoglu, Ilker Y.Dresden University of Technology,Friedrich-Alexander University Erlangen-Nürnberg
(författare)
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Gollwitzer, StephanieUniversity Hospital Erlangen
(författare)
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Hamer, Hajo M.University Hospital Erlangen
(författare)
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Gerner, Stefan T.University Hospital Erlangen,Justus Liebig University Giessen
(författare)
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Döppner, Thorsten R.Justus Liebig University Giessen
(författare)
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Rummel, ChristophJustus Liebig University Giessen
(författare)
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Englund, ElisabetLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-een
(författare)
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Heimke-Brinck, RalphFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Borst, TobiasFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Daniel, ChristophFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Amann, KerstinFriedrich-Alexander University Erlangen-Nürnberg
(författare)
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Schlötzer-Schrehardt, UrsulaUniversity Hospital Erlangen
(författare)
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Tonchev, Anton B.Medical University of Varna
(författare)
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Roessler, KarlFriedrich-Alexander University Erlangen-Nürnberg,University of Vienna
(författare)
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Schwab, StefanUniversity Hospital Erlangen
(författare)
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Bergmann, OlafKarolinska Institutet,Karolinska Institute,University Medical Center Göttingen,Dresden University of Technology
(författare)
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Rizzoli, Silvio O.University Medical Center Göttingen
(författare)
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Huttner, Hagen B.University Hospital Erlangen,Justus Liebig University Giessen
(författare)
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Dresden University of TechnologyUniversity Hospital Erlangen
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Frontiers in Neuroscience171662-4548
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Roeder, Sebastia ...
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Bonnin, Elisa A.
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Wu, Ting Di
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Guerquin-Kern, J ...
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Jabari, Samir
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Brandner, Sebast ...
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visa fler...
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Eyüpoglu, Ilker ...
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Gollwitzer, Step ...
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Hamer, Hajo M.
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Gerner, Stefan T ...
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Döppner, Thorste ...
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Rummel, Christop ...
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Englund, Elisabe ...
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Heimke-Brinck, R ...
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Borst, Tobias
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Daniel, Christop ...
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Amann, Kerstin
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Schlötzer-Schreh ...
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Tonchev, Anton B ...
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Roessler, Karl
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Schwab, Stefan
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Bergmann, Olaf
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Rizzoli, Silvio ...
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Huttner, Hagen B ...
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och Neurovetenskaper
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Lunds universitet
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