Assessment of brain metabolite correlates of adeno-associated virus-mediated over-expression of human alpha-synuclein in cortical neurons by in vivo 1H-MR spectroscopy at 9.4 T

In this study, we used proton-localized spectroscopy (H-1-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein (ct-syn) over-expression. Our goal was to find out if the increased alpha-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with MV vectors encoding for human alpha-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector treated control group and a third group of uninjected animals were used as naive controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p=0.005) were specifically lower in the alpha-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that alpha-syn over-expression in cortical neurons did not result in neurodegeneration in this model.