title: Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.
abstract: Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease.
  
  
  METHODS
  Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain.
  
  
  RESULTS
  We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05.
  
  
  CONCLUSIONS
  Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease.
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland Department of Clinical Neurophysiology, Turku University Hospital and University of Turku, Turku, Finland; and jtjout@utu.fi.
authors.forename: Juho
authors.initials: J
authors.lastname: Joutsa
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Seppänen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Noponen
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Kaasinen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004298:Dopamine / Q000737:chemistry*; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes / Q000737:chemistry; D008024:Ligands; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging*; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging*; D011903:Raphe Nuclei / Q000000981:diagnostic imaging*; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry; D013788:Thalamus / Q000000981:diagnostic imaging*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014326:Tropanes / Q000737:chemistry
chemical_list: D007457:Iodine Radioisotopes; D008024:Ligands; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D004298:Dopamine
keywords: SPECT; dopamine; midbrain; raphe nuclei; serotonin