In vivo NMR studies of regional cerebral energetics in MPTP model of Parkinson's disease: recovery of cerebral metabolism with acute levodopa treatment

In this study, we have evaluated cerebral atrophy, neurometabolite homeostasis, and neural energetics in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) model of Parkinson's disease. In addition, the efficacy of acute L-DOPA treatment for the reversal of altered metabolic functions was also evaluated. Cerebral atrophy and neurochemical profile were monitored in vivo using MRI and H-1 MR Spectroscopy. Cerebral energetics was studied by H-1-[C-13]-NMR spectroscopy in conjunction with infusion of C-13 labeled [1,6-C-13(2)] glucose or [2-C-13] acetate. MPTP treatment led to reduction in paw grip strength and increased level of GABA and myoinositol in striatum and olfactory bulb. C-13 Labeling of glutamate-C4 (1.93 +/- 0.24 vs. 1.48 +/- 0.06 mu mol/g), GABAC2 (0.24 +/- 0.04 vs. 0.18 +/- 0.02 mu mol/g) and glutamaine-C4 0.26 +/- 0.04 vs. 0.20 +/- 0.04 mu mol/ g) from [1,6-C-13(2)] glucose was found to be decreased with MPTP exposure in striatum as well as in other brain regions. However, glutamine-C4 labeling from [2-C-13] acetate was found to be increased in the striatum of the MPTP-treated mice. Acute L-DOPA treatment failed to normalize the increased ventricular size and level of metabolites but recovered the paw grip strength and C-13 labeling of amino acids from [1,6-C-13(2)] glucose and [2-C-13] acetate in MPTP-treated mice. These data indicate that brain energy metabolism is impaired in Parkinson's disease and acute L-DOPA therapy could temporarily recover the cerebral metabolism.