Impairment of energy metabolism is a key feature of Huntington disease (HD). Recently, University of Minnesota researchers reported longitudinal neurochemical changes in R6/2 mice measured by in-vivo proton magnetic resonance spectroscopy (1H MRS; Zacharoff et al, 2012). Here, they present similar 1H MRS measurements at an early stage in the milder Q111 mouse model. In addition, they measured the concentration of ATP and inorganic phosphate (Pi), key energy metabolites not accessible with 1H MRS, using 31P MRS both in Q111 and in R6/2 mice. Significant changes in striatal creatine and phosphocreatine were observed in Q111 mice at 6 weeks relative to control, and these changes were largely reversed at 13 weeks. No significant change was detected in ATP concentration, in either HD mouse, compared with control. Calculated values of [ADP], phosphorylation potential, relative rate of ATP synthase (v/Vmax(ATP)), and relative rate of creatine kinase (v/Vmax(CK)) were calculated from the measured data. ADP concentration and v/Vmax(ATP) were increased in Q111 mice at 6 weeks, and returned close to normal at 13 weeks. In contrast, these parameters were normal in R6/2 mice. These results suggest that early changes in brain energy metabolism are followed by compensatory shifts to maintain energetic homeostasis from early ages through manifest disease.
In-vivo 1H MR spectra acquired from the striatum of Q111 and wild-type (WT) mice at 13 weeks. STEAM, echo time=2 ms, repetition time (TR)=5 seconds, VOI=8.5 μL, number of transients=240. No water signal removal or baseline corrections were applied. Insets: coronal and sagittal FSE MRI with a typical VOI selection. MR, magnetic resonance; VOI, volumes of interest; FSE MRI, fast spin-echo magnetic resonance imaging; Ala, alanine; Asc, ascorbate; Cr, creatine; GABA, γ-aminobutyric acid; Glu, glutamate; Gln, glutamine; GSH, glutathione; GPC, glycerophosphocholine; Ins, inositol; Lac, lactate; NAA, N-acetylaspartate; PCr, phosphocholine; Tau, taurine.
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Reference
Tkac I, Henry P, Zacharoff L, Wedel M, Gong W, Deelchand DK, Li T, Dubinsky JM. (2012) Homeostatic adaptations in brain energy metabolism in mouse models of Huntington disease. J Cereb Blood Flow Metab 32(11), 1977-88. [article]