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Tracking cell turnover in human brain using 15N-thymidine imaging mass spectrometry
Sebastian S Roeder1,2, Elisa A Bonnin3, Ting-Di Wu4
1Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
Frontiers in Neuroscience
|October 23, 2023
Summary
This study introduces a safe method using 15N-thymidine to track new cell generation in the adult human brain. While neurogenesis was detected in glioblastoma tissue, it was not found in the hippocampus, suggesting low rates in this region.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Neurogenesis, the generation of new neurons, is crucial for brain development and function.
- While adult neurogenesis is established in rodents, its extent in humans, particularly in the hippocampus, remains debated due to methodological limitations.
Purpose of the Study:
- To demonstrate a safe and effective method for quantifying adult human neurogenesis using in vivo 15N-thymidine labeling.
- To investigate the presence and magnitude of neurogenesis in specific regions of the adult human brain.
Main Methods:
- Administered 15N-thymidine, a non-hazardous thymidine analog, to adult human patients undergoing surgery.
- Quantified 15N incorporation into newly synthesized DNA at the single-cell level using Multiple-isotype imaging mass spectrometry (MIMS) on resected brain tissue.
- Confirmed method validity by detecting 15N-positive leukocytes in blood samples.
Main Results:
- Successfully identified 15N-positive neural cells in glioblastoma tissue, indicating active cell division and proliferation.
- No 15N-thymidine uptake was detected in 2,000 analyzed dentate gyrus neurons from epilepsy patient hippocampus, suggesting very low neurogenesis rates.
- Methodological considerations, including sample size and labeling duration, may have influenced the detection of low-rate neurogenesis.
Conclusions:
- In vivo 15N-thymidine labeling combined with MIMS is a viable approach to study adult human neurogenesis.
- The study provides evidence for limited neurogenesis in the adult human hippocampus, contrasting with findings in rodents.
- This novel methodology opens avenues for broad research into brain physiology and pathology, including conditions like microcephaly.
