title: Metabolic profiling of dividing cells in live rodent brain by proton magnetic resonance spectroscopy (1HMRS) and LCModel analysis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: June-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York, United States of America.
authors.forename: Hedok
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York, United States of America.
authors.forename: Rany
authors.initials: R
authors.lastname: Makaryus
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York, United States of America.
authors.forename: S David
authors.initials: SD
authors.lastname: Smith
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: Kasim
authors.initials: K
authors.lastname: Sayed
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, New York, United States of America.
authors.forename: Tian
authors.initials: T
authors.lastname: Feng
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Holland
authors.affiliation: Department of Biomedical Sciences, Bio-Imaging Laboratory, University of Antwerp, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
authors.affiliation: Neuropsychiatry Laboratory, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Bolwig
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
authors.affiliation: Department of Anesthesiology, Stony Brook Medicine, Stony Brook, New York, United States of America; Department of Radiology, Stony Brook Medicine, Stony Brook, New York, United States of America.
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D055442:Metabolome / Q000502:physiology*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley