Are dopamine receptor and transporter changes in Rett syndrome reflected in Mecp2-deficient mice?

Autor: Wong DF; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Psychiatry, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: dfwong@jhu.edu., Blue ME; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205, United States; Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Department of Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: blue@kennedykrieger.org., Brašić JR; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: brasic@jhmi.edu., Nandi A; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: anandi1@jhmi.edu., Valentine H; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: hvalent2@jhmi.edu., Stansfield KH; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: kirstie.stansfield@gmail.com., Rousset O; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: Olivier@jhu.edu., Bibat G; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205, United States. Electronic address: Bibat@kennedykrieger.org., Yablonski ME; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205, United States. Electronic address: mcyablon@verizon.net., Johnston MV; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205, United States; Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: Johnston@kennedkrieger.org., Gjedde A; Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States; Departments of Clinical Research and Nuclear Medicine, Odense University Hospital, University of Southern Denmark, 5000 Odense, Denmark. Electronic address: albert.gjedde@rsyd.dk., Naidu S; Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Baltimore, MD 21205, United States; Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States. Electronic address: naidu@kennedykrieger.org.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2018 Sep; Vol. 307, pp. 74-81. Date of Electronic Publication: 2018 May 18.
DOI: 10.1016/j.expneurol.2018.05.019
Abstrakt: We tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D 2 receptors (D 2 R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D 1 R and D 2 R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D 2 R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D 2 R density of 7-10 week-old hemizygous (Mecp2-null) and heterozygous (HET) mice compared to wild type (WT) mice. With age, the density of D 2 R declined in WT mice but not HET mice. 3) In contrast, postmortem autoradiography revealed no group differences in the density of D 1 R and D 2 R in the caudate and putamen of RTT versus normal control subjects. 4) In humans and in the mouse model, PET revealed only marginal group differences in DAT. The results confirm that dopaminergic dysfunction in RTT is also present in Mecp2-deficient mice and that reductions in D 2 R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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