title: In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers.
abstract: BACKGROUND
  We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome.
  
  
  METHODS
  All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter).
  
  
  RESULTS
  FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum.
  
  
  CONCLUSIONS
  Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene.
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Andre C
authors.initials: AC
authors.lastname: Felicio
authors.forename: Katherine
authors.initials: K
authors.lastname: Dinelle
authors.forename: Pankaj A
authors.initials: PA
authors.lastname: Agarwal
authors.forename: Jessamyn
authors.initials: J
authors.lastname: McKenzie
authors.forename: Nicole
authors.initials: N
authors.lastname: Heffernan
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Road
authors.forename: Silke
authors.initials: S
authors.lastname: Appel-Cresswell
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Michael
authors.initials: M
authors.lastname: Schulzer
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
mesh_terms: D000328:Adult; D000814:Aniline Compounds; D003342:Corpus Striatum / Q000000981:diagnostic imaging; D003863:Depression / Q000000981:diagnostic imaging / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D000072159:Dynactin Complex; D005462:Fluorine Radioisotopes; D006801:Humans; D007040:Hypoventilation / Q000000981:diagnostic imaging / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D049268:Positron-Emission Tomography; D020891:Raclopride; D012701:Serotonin / Q000008:administration & dosage*; D013440:Sulfides; D013747:Tetrabenazine / Q000031:analogs & derivatives; D014055:Tomography, Emission-Computed; D057177:TDP-43 Proteinopathies
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D005462:Fluorine Radioisotopes; D008869:Microtubule-Associated Proteins; D013440:Sulfides; D012701:Serotonin; C032811:dihydrotetrabenazine; D020891:Raclopride; D004298:Dopamine; D013747:Tetrabenazine
keywords: Perry syndrome; dopaminergic dysfunction; dynactin gene; positron emission tomography; serotonergic dysfunction