Single-dose L-dopa increases upper brainstem GABA in Parkinson's disease: A preliminary study

Purpose: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder, characterized by the dysfunction between dopaminergic and GABAergic neuronal activities. Dopamine (DA) replacement by its precursor L-dopa remains the primary treatment for PD. In this preliminary study, we test the hypotheses that GABA+ levels would be lower in PD patients than controls, and normalized by L-dopa. Methods: Eleven PD patients and eleven age-and gender-matched healthy controls underwent a ¹H-MRS scan of the upper brainstem using a J-difference-edited sequence to resolve signals of GABA. PD patients did not take all dopaminergic medicines for at least twelve hours prior to the first scan, and were scanned again after resuming L -dopa (pre- and post-L-dopa). MRS data were processed using the Gannet. Differences of GABA+ (GABA, macromolecules, and homocarnosine) levels within-subject (PD: pre- and post-L-dopa) and between-subjects (HC vs. PD-pre or PD-post) were tested using linear mixed-effects models with Holm-Bonferroni correction applied to pairwise comparisons. Results: Significant increased GABA+ levels were observed in the upper brainstem of PD patients post-L-dopa compared with pre-L-dopa (p < 0.001). Patients' GABA+ levels before administration of L-dopa were significantly lower than HCs (p = 0.001). Increased GABA+ level by administration of L-dopa in PD patients (post-L-dopa) was lower compared with HCs, but not significantly (p = 0.52). Conclusion: Increased GABA+ levels were present in the upper brainstem with PD patients post-L-dopa, suggesting dopaminergic therapy capable of improving dopamine may improve the GABA+ levels in the upper brainstem, thereby achieving the effect of modulating the GABAergic system in the treatment of PD.