Abstract
PurposeThe serotonin transporter (SERT) is a biochemical marker for monoaminergic signaling in brain and has been suggested to be involved inthe pathophysiology of Parkinson’s disease (PD). The aim of this PET study was to examine SERT availability in relevant brain regions in early stages ofnon-depressed PD patients.MethodsIn a cross-sectional study, 18 PD patients (13 M/5F, 64 ± 7 years, range 46–74 years, disease duration 2.9 ± 2.6 years; UPDRS motor 21.9 ± 5.2) and 20 age- and gender-matched healthy control (HC) subjects (15 M/5F, 61 ± 7 years, range 50–72 years) were included. In a subsequent longitudinal phase, ten of the PD patients (7 M/3F, UPDRS motor 20.6 ± 6.9) underwent a second PET measurement after 18–24 months. After a 3-T MRI acquisition, baseline PET measurements were performed with [11C]MADAM using a high-resolution research tomograph. The non-displaceablebinding potential (BPND) was chosen as the outcome measure and was estimated at voxel level on wavelet-aided parametric images, by using the Logan graphical analysis and the cerebellum as reference region. A molecular template was generated to visualize and define different subdivisions of the raphe nuclei in the brainstem. Subortical and cortical regions of interest were segmented using FreeSurfer. Univariate analyses and multivariate network analyses were performed on the PET data.ResultsThe univariate region-based analysis showed no differences in SERT levels when the PD patients were compared with the HC neither at baseline or after 2 years of follow-up. The multivariate network analysis also showed no differences at baseline. However, prominent changes in integration and segregation measures were observed at follow-up, indicating a disconnection of the cortical and subcortical regions from the three nuclei of the raphe.ConclusionWe conclude that the serotoninergic system in PD patients seems to become involved with a network dysregulation as the disease progresses, suggesting a disturbed serotonergic signaling from raphe nuclei to target subcortical and cortical regions.
Highlights
Parkinson’s disease (PD) is a multidomain neurodegenerative disease with a wide phenotypic expression
In early PD patients, serotonin markers including its transporter (SERT) availabilities in subcortical regions were lower than healthy control (HC) by 11.2% in the caudate, 11.8% in the putamen and 7.7% in the pallidus (Fig. 2)
In all subdivisions of raphe nuclei, SERT availabilities were lower in PD than in HC only by 2.8% on average (Fig. 2)
Summary
Parkinson’s disease (PD) is a multidomain neurodegenerative disease with a wide phenotypic expression. The clinical expression of such symptoms is likely related to the accumulation of misfolded proteins (alpha-synuclein, tau, and amyloid) [2, 3] as well as to patterns of cortical atrophy [4]. Molecular changes in different neurotrasmitter systems are related to the expression of clinical phenotypes. The involvement of different serotoninergic nuclei of the raphe (dorsal, medial, and caudal) has been reported in postmortem brainstem samples from PD patients [6]. Another postmortem study demonstrated that different serotonin markers including its transporter (SERT) were reduced in PD patients as compared with healthy controls, with a prevalent involvement of the caudate over the putamen [7]
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