Putaminal y-aminobutyric acid modulates motor response to dopaminergic therapy in Parkinson's Disease
7th June 2021
Aline D. Seger, Ezequiel Farrher, Christopher E.J. Doppler, Ana Gogishvili, Wieland A. Worthoff, Christian P. Filss, Michael T. Barbe, Florian Holtbernd, N. Jon Shah, Gereon R. Fink, Michael Sommerauer
Parkinson’s disease (PD) is a neurodegenerative disorder that prominently affects the basal-ganglia motor system, manifesting in symptoms such as bradykinesia, tremor and rigidity.
Although there is currently no cure for PD, motor symptoms typically show a considerable response to dopaminergic treatment. Consequently, dopaminergic responsiveness is a key feature in the current diagnostic criteria for PD.
However, despite dopamine being the pivotal neurotransmitter facilitating motor execution in the basal ganglia circuitry, other neurotransmitters are known to be involved, and alterations in nondopaminergic brain metabolites are also associated with PD.
Notably, several animal and human studies have shown that in PD, the concentration of γ-aminobutyric acid (GABA) is significantly elevated in selected brain areas.
Consequently, the aim of this study was to determine whether there is an association between putaminal y-aminobutyric acid (GABA) levels and dopaminergic motor response.
Nineteen PD patients and thirteen healthy controls (HC) took part in the study which used ultra-high field proton magnetic resonance spectroscopy to assess putaminal GABA levels. Motor performance was evaluated using the Movement Disorder Society—Unified Parkinson's Disease Rating Scale, Part III, in the ON and OFF states, and statistical analysis comprised group comparisons, correlation analysis, and multiple linear regression.
The results showed that GABA levels were significantly higher in PD patients than HCs, and, furthermore, GABA levels were independent predictors of absolute and relative dopaminergic treatment response. In light of this, future studies are needed to further explore the interplay of nondopaminergic neurotransmitter systems on dopaminergic function.
It is anticipated that a better understanding of these complex interactions may eventually facilitate individualised pharmacological treatment strategies for PD patients exhibiting poor motor response to dopaminergic therapy.
The figure above shows the
1H-MRS spectra of a healthy control (HC) and a Parkinson's disease (PD) patient.
Original publication