Metabolic profiling of dividing cells in live rodent brain by proton magnetic resonance spectroscopy (1HMRS) and LCModel analysis

• Published in: PloS one Vol. 9; no. 5; p. e94755
• Main Authors: Park, June-Hee, Lee, Hedok, Makaryus, Rany, Yu, Mei, Smith, S David, Sayed, Kasim, Feng, Tian, Holland, Eric, Van der Linden, Annemie, Bolwig, Tom G, Enikolopov, Grigori, Benveniste, Helene
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.05.2014; Public Library of Science (PLoS)
• Subjects: Algorithms; Anesthesiology; Animals; Apoptosis; Aspartate; Biology and Life Sciences; Brain; Brain - metabolism; Brain cancer; Cell division; Correlation analysis; Droplets; Electroconvulsive therapy; Female; Hippocampus; Histology; Laboratory animals; Lactic acid; Lipids; Magnetic resonance; Magnetic resonance imaging; Magnetic resonance spectroscopy; Medical imaging; Medicine; Medicine and Health Sciences; Metabolism; Metabolites; Metabolome - physiology; Mice; Neurogenesis; Neuroimaging; Nuclear magnetic resonance spectroscopy; Physical Sciences; Platelet-derived growth factor; Positron emission; Positron emission tomography; Profiling; Proton magnetic resonance; Proton Magnetic Resonance Spectroscopy - methods; Psychiatry; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Resonance; Spectra; Spectral analysis; Spectral signatures; Spectroscopy; Spectrum analysis; Stem cells; Tumors; Wavelet transforms; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094755

Dividing cells can be detected in the live brain by positron emission tomography or optical imaging. Here we apply proton magnetic resonance spectroscopy (1HMRS) and a widely used spectral fitting algorithm to characterize the effect of increased neurogenesis after electroconvulsive shock in the live rodent brain via spectral signatures representing mobile lipids resonating at ∼1.30 ppm. In addition, we also apply the same 1HMRS methodology to metabolically profile glioblastomas with actively dividing cells growing in RCAS-PDGF mice. 1HMRS metabolic profiles were acquired on a 9.4T MRI instrument in combination with LCModel spectral analysis of: 1) rat brains before and after ECS or sham treatments and 2) RCAS-PDGF mice with glioblastomas and wild-type controls. Quantified 1HMRS data were compared to post-mortem histology. Dividing cells in the rat hippocampus increased ∼3-fold after ECS compared to sham treatment. Quantification of hippocampal metabolites revealed significant decreases in N-acetyl-aspartate but no evidence of an elevated signal at ∼1.3 ppm (Lip13a+Lip13b) in the ECS compared to the sham group. In RCAS-PDGF mice a high density (22%) of dividing cells characterized glioblastomas. Nile Red staining revealed a small fraction (3%) of dying cells with intracellular lipid droplets in the tumors of RCAS-PDGF mice. Concentrations of NAA were lower, whereas lactate and Lip13a+Lip13b were found to be significantly higher in glioblastomas of RCAS-PDGF mice, when compared to normal brain tissue in the control mice. Metabolic profiling using 1HMRS in combination with LCModel analysis did not reveal correlation between Lip13a+Lip13b spectral signatures and an increase in neurogenesis in adult rat hippocampus after ECS. However, increases in Lip13a+Lip13b were evident in glioblastomas suggesting that a higher density of actively dividing cells and/or the presence of lipid droplets is necessary for LCModel to reveal mobile lipids.