title: Proton MR spectroscopy of neural stem cells: does the proton-NMR peak at 1.28 ppm function as a biomarker for cell type or state?
abstract: Recently, a peak at 1.28 ppm in proton magnetic resonance spectroscopy ((1)H-MRS) of neural stem cells (NSCs) was introduced as a noninterventional biomarker for neurogenesis in vivo. This would be an urgently needed requisite for translational studies in humans regarding the beneficial role of adult neurogenesis for the structural and functional integrity of the brain. However, many concerns have risen about the validity of the proposed signal as a specific marker for NSCs. The peak has also been related to cell-type-independent phenomena such as apoptosis or necrosis. Thus, we compared the 1.28-ppm peak in various immature stem cell populations, including embryonic stem cells, mouse embryonic fibroblasts, embryonic stem cell- and induced pluripotent stem cell-derived NSCs, ex vivo isolated embryonic NSCs, as well as mature and tumor cell types from different germ layers. To correlate the integral peak intensity with cell death, we induced both apoptosis with camptothecin and necrosis with sodium azide. A peak at 1.28 ppm was found in most cell types, and in most, but not all, NSCH cultures, demonstrating no specificity for NSCs. The intensities of the 1.28-ppm resonance significantly correlated with the rate of apoptosis, but not with the rate of necrosis, cell cycle phase distribution, cell size, or type. Multiple regression analysis displayed a significant predictive value of the peak intensity for apoptosis only. In this context, its specificity for apoptosis as a major selection process during neurogenesis may suggest this resonance as an indirect marker for neurogenesis in vivo.
authors.affiliation: Department of Neurology and Center for RegenerativeTherapies Dresden (CRTD), Dresden University of Technology, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Kai F
authors.initials: KF
authors.lastname: Loewenbrück
authors.forename: Beate
authors.initials: B
authors.lastname: Fuchs
authors.forename: Andreas
authors.initials: A
authors.lastname: Hermann
authors.forename: Moritz
authors.initials: M
authors.lastname: Brandt
authors.forename: Annett
authors.initials: A
authors.lastname: Werner
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
authors.forename: Sigrid
authors.initials: S
authors.lastname: Schwarz
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwarz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism*; D002449:Cell Aggregation; D002453:Cell Cycle; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D011522:Protons
chemical_list: D015415:Biomarkers; D011522:Protons