TY - JOUR
T1 - Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H NMR spectroscopy
AU - Tkac, Ivan
AU - Dubinsky, Janet M.
AU - Keene, C. Dirk
AU - Gruetter, Rolf
AU - Low, Walter C.
PY - 2007/3
Y1 - 2007/3
N2 - The neurochemical profile of the striatum of R6/2 Huntington's disease mice was examined at different stages of pathogenesis using in vivo1H NMR spectroscopy at 9.4 T. Between 8 and 12 weeks, R6/2 mice exhibited distinct changes in a set of 17 quantifiable metabolites compared with littermate controls. Concentrations of creatine, glycerophosphorylcholine, glutamine and glutathione increased and N-acetylaspartate decreased at 8 weeks. By 12 weeks, concentrations of phosphocreatine, taurine, ascorbate, glutamate, and myo-inositol increased and phophorylethanolamine decreased. These metabolic changes probably reflected multiple processes, including compensatory processes to maintain homeostasis, active at different stages in the development of HD. The observed changes in concentrations suggested impairment of neurotransmission, neuronal integrity and energy demand, and increased membrane breakdown, gliosis, and osmotic and oxidative stress. Comparisons between metabolite concentrations from individual animals clearly distinguished HD transgenics from non-diseased littermates and identified possible markers of disease progression. Metabolic changes in R6/2 striata were distinctly different from those observed previously in the quinolinic acid and 3NP models of HD. Longitudinal monitoring of changes in these metabolites may provide quantifiable measures of disease progression and treatment effects in both mouse models of HD and patients.
AB - The neurochemical profile of the striatum of R6/2 Huntington's disease mice was examined at different stages of pathogenesis using in vivo1H NMR spectroscopy at 9.4 T. Between 8 and 12 weeks, R6/2 mice exhibited distinct changes in a set of 17 quantifiable metabolites compared with littermate controls. Concentrations of creatine, glycerophosphorylcholine, glutamine and glutathione increased and N-acetylaspartate decreased at 8 weeks. By 12 weeks, concentrations of phosphocreatine, taurine, ascorbate, glutamate, and myo-inositol increased and phophorylethanolamine decreased. These metabolic changes probably reflected multiple processes, including compensatory processes to maintain homeostasis, active at different stages in the development of HD. The observed changes in concentrations suggested impairment of neurotransmission, neuronal integrity and energy demand, and increased membrane breakdown, gliosis, and osmotic and oxidative stress. Comparisons between metabolite concentrations from individual animals clearly distinguished HD transgenics from non-diseased littermates and identified possible markers of disease progression. Metabolic changes in R6/2 striata were distinctly different from those observed previously in the quinolinic acid and 3NP models of HD. Longitudinal monitoring of changes in these metabolites may provide quantifiable measures of disease progression and treatment effects in both mouse models of HD and patients.
KW - Huntington's disease
KW - In vivo H NMR spectroscopy
KW - Neurochemical profile
KW - Quantification
KW - Transgenic mice
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U2 - 10.1111/j.1471-4159.2006.04323.x
DO - 10.1111/j.1471-4159.2006.04323.x
M3 - Article
C2 - 17217418
AN - SCOPUS:33846970909
SN - 0022-3042
VL - 100
SP - 1397
EP - 1406
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -