Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Aug;29(9):1197-201.
doi: 10.1002/mds.25893. Epub 2014 May 5.

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

Andre C Felicio  1 , Katherine Dinelle, Pankaj A Agarwal, Jessamyn McKenzie, Nicole Heffernan, Jeremy D Road, Silke Appel-Cresswell, Zbigniew K Wszolek, Matthew J Farrer, Michael Schulzer, Vesna Sossi, A Jon Stoessl
Affiliations

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

Andre C Felicio et al. Mov Disord. 2014 Aug.

Abstract

Introduction: 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.

Keywords: Perry syndrome; dopaminergic dysfunction; dynactin gene; positron emission tomography; serotonergic dysfunction.

PubMed Disclaimer

Conflict of interest statement

Financial disclosure/conflict of interest concerning the research related to the manuscript: none

Figures

Figure 1
Figure 1
Figure 1. [¹¹C]-DASB positron emission tomography study in an affected subject with genetically-proven Perry syndrome compared to healthy control subjects (n=6). Bar charts represent (A) Cortical areas, (B) Subcortical areas, and (C) Brainstem. Legend: Amyg = amygdala; AntCing = anterior cingulate; AntIns = anterior insula; Caud = caudate; DLPFC = dorsolateral prefrontal cortex; HypTh = hypothalamus; MidBr = midbrain; OFC = orbitofrontal cortex; PostCing = posterior cingulate; Put = putamen; SN = substantia nigra; Thal = thalamus; VS = ventral striatum. An asterisk (*) denotes values outside 2 standard deviations compared to control values. For midline structures (pons/midbrain/medulla) only a single value is reported.
Figure 1
Figure 1
Figure 1. [¹¹C]-DASB positron emission tomography study in an affected subject with genetically-proven Perry syndrome compared to healthy control subjects (n=6). Bar charts represent (A) Cortical areas, (B) Subcortical areas, and (C) Brainstem. Legend: Amyg = amygdala; AntCing = anterior cingulate; AntIns = anterior insula; Caud = caudate; DLPFC = dorsolateral prefrontal cortex; HypTh = hypothalamus; MidBr = midbrain; OFC = orbitofrontal cortex; PostCing = posterior cingulate; Put = putamen; SN = substantia nigra; Thal = thalamus; VS = ventral striatum. An asterisk (*) denotes values outside 2 standard deviations compared to control values. For midline structures (pons/midbrain/medulla) only a single value is reported.
Figure 1
Figure 1
Figure 1. [¹¹C]-DASB positron emission tomography study in an affected subject with genetically-proven Perry syndrome compared to healthy control subjects (n=6). Bar charts represent (A) Cortical areas, (B) Subcortical areas, and (C) Brainstem. Legend: Amyg = amygdala; AntCing = anterior cingulate; AntIns = anterior insula; Caud = caudate; DLPFC = dorsolateral prefrontal cortex; HypTh = hypothalamus; MidBr = midbrain; OFC = orbitofrontal cortex; PostCing = posterior cingulate; Put = putamen; SN = substantia nigra; Thal = thalamus; VS = ventral striatum. An asterisk (*) denotes values outside 2 standard deviations compared to control values. For midline structures (pons/midbrain/medulla) only a single value is reported.
Figure 2
Figure 2
18F-6-fluoro-L-dopa (FDOPA), (+)-11C-dihydrotetrabenazine (DTBZ), 11C-raclopride (RAC), and 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) imaging panel showing a genetically-proven Perry syndrome subject (right) as compared to an approximately age-matched control (left). FDOPA uptake (A) and DTBZ binding (B) are reduced in the Perry subject compared to the control subject (left). In contrast, RAC binding is normal in the Perry subject (C). There are widespread reductions in DASB binding in the Perry subject (D). (A) through (C) are axial images, (D) is sagittal.
See this image and copyright information in PMC

References

    1. Farrer MJ, Hulihan MM, Kachergus JM, et al. DCTN1 mutations in Perry syndrome. Nat Genet. 2009;41:163–165. - PMC - PubMed
    1. Perry TL, Wright JM, Berry K, Hansen S, Perry TL., Jr Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. Neurology. 1990;40:1882–1887. - PubMed
    1. Lechevalier B, Chapon F, Defer G, et al. Perry and Purdy's syndrome (familial and fatal parkinsonism with hypoventilation and athymhormia) Bull Acad Natl Med. 2005;189:481–490. - PubMed
    1. Nandhagopal R, Kuramoto L, Schlzer M, et al. Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease. Brain. 2011;134:3290–3298. - PubMed
    1. Vingerhoets FJ, Snow BJ, Lee CS, Schulzer M, Mak E, Calne DB. Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism. Ann Neurol. 1994;36:759–764. - PubMed

Publication types

MeSH terms

Supplementary concepts