In vivo Illustration of Altered Dopaminergic and GABAergic Systems in Early Parkinson's Disease

Hirotsugu Takashima; Tatsuhiro Terada; Tomoyasu Bunai; Takashi Matsudaira; Tomokazu Obi; Yasuomi Ouchi

doi:10.3389/fneur.2022.880407

In vivo Illustration of Altered Dopaminergic and GABAergic Systems in Early Parkinson's Disease

Front Neurol. 2022 May 17:13:880407. doi: 10.3389/fneur.2022.880407. eCollection 2022.

Authors

Hirotsugu Takashima^{1

2}, Tatsuhiro Terada^{1

2}, Tomoyasu Bunai², Takashi Matsudaira^{1

2}, Tomokazu Obi¹, Yasuomi Ouchi^{2

3}

Affiliations

¹ Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
² Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³ Hamamatsu PET Imaging Center, Hamamatsu Medical Photonics Foundation, Hamamatsu, Japan.

Abstract

Background: Changes in γ-aminobutyric acid (GABA) function are noted in patients with Parkinson's disease (PD) who have some non-motor impairments. However, dopamine-related GABA function and GABA-related cognitive changes are still unclear.

Methods: Thirteen drug-naive early-stage PD patients underwent a series of PET scans with [¹¹C]flumazenil(FMZ) and [¹¹C]CFT. The [¹¹C]FMZ binding potential (BP_ND) derived from a Logan plot analysis was compared between PD patients and age-matched controls. The [¹¹C]CFT radioactivity relative to the cerebellar counterpart was estimated as a semiquantitative value [¹¹C]CFT SUVR. Correlations between [¹¹C]FMZ BP_ND and [¹¹C]CFT SUVR in the same region of interest were also examined.

Results: In patients in the PD group, [¹¹C]CFT SUVR was significantly lower in the putamen. The levels of [¹¹C]FMZ BP_ND in the cerebral cortex (frontal lobe dominancy) and the affected-side putamen were also reduced. In addition, [¹¹C]CFT SUVR was negatively correlated with the [¹¹C]FMZ BP_ND level in the affected-side putamen. In patients in the PD group, the total frontal assessment battery (FAB) score was positively correlated with the [¹¹C]FMZ BP_ND in the frontal region.

Conclusion: GABAergic dysfunction coexists with dopaminergic loss not only in the putamen but also over the extrastriatal region in patients with early PD and is related to frontal dysfunction. The negative correlation of [¹¹C]CFT SUVR with [¹¹C]FMZ BP_ND in the affected putamen suggests that a greater dopaminergic demise would decelerate GABA release (or an increase in tracer binding), resulting in persistent failure of the GABAergic system in PD patients.

Keywords: CFT; GABA; Parkinson's disease (PD); flumazenil; frontal assessment battery (FAB); positron emission tomography.