Response to: Comment on ‘Human adult neurogenesis across the ages: An immunohistochemical study’

Dennis, Claude; Suh, Lisa S.; Rodriguez, Michael; Kril, Jillian J.; Sutherland, Greg T.

doi:10.1111/nan.12394

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…However, studies in mice showed that AHN is exponentially decreasing after 7 weeks of age till about 4 months—during peak conditions for reproduction—and leveling off afterwards (Ben Abdallah et al, 2010). A strong decline during the first year of life has now been documented repeatedly for humans (Knoth et al, 2010; Dennis et al, 2016, 2017). Weissleder et al (2016) have reported a further decrease from years 21 till 91, yet starting from a low level.…”

Section: Ahn Is Strongly Down-regulated But Is Bottoming Out After Twmentioning

confidence: 89%

Evolutionary Shaping of Adult Hippocampal Neurogenesis in Mammals–Cognitive Gain or Developmental Priming of Personality Traits?

Lipp

2017

Front. Neurosci.

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Section: Ahn Is Strongly Down-regulated But Is Bottoming Out After Twmentioning

confidence: 89%

Evolutionary Shaping of Adult Hippocampal Neurogenesis in Mammals–Cognitive Gain or Developmental Priming of Personality Traits?

Lipp

2017

Front. Neurosci.

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“…Our data with glioblastoma tissue resected from an adult human patient demonstrate that mitotically active cells and their progeny can be detected by this approach. In the case of the hippocampal tissue resected from an epilepsy patient, the lack of detection of 15 N-thymidine-labeled neurons in the granule cell layer among the 500 neurons analyzed in two 200-nm sections was to be expected if the rate of generation of newborn neurons in the adult human dentate gyrus is indeed as low as reported (Knoth et al, 2010;Spalding et al, 2013;Bergmann et al, 2015;Dennis et al, 2017;Cipriani et al, 2018;Sorrells et al, 2018). Such a low probability poses a great challenge for the "standard" approach presented in Figure 3, in light of the sophisticated nature of MIMS analysis, including the duration of image acquisition, and the number of cells that can be analyzed in a single scan (see Materials and methods and Supplementary Figure 7).…”

Section: Discussionmentioning

confidence: 91%

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry

Roeder,

Bonnin,

et al. 2023

Front. Neurosci.

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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.

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Response to: Comment on ‘Human adult neurogenesis across the ages: An immunohistochemical study’

Cited by 2 publications

References 14 publications

Evolutionary Shaping of Adult Hippocampal Neurogenesis in Mammals–Cognitive Gain or Developmental Priming of Personality Traits?

Evolutionary Shaping of Adult Hippocampal Neurogenesis in Mammals–Cognitive Gain or Developmental Priming of Personality Traits?

Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry

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