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

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

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 D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice...

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Published in:Experimental neurology Vol. 307; pp. 74 - 81
Main Authors: Wong, Dean F., Blue, Mary E., Brašić, James R., Nandi, Ayon, Valentine, Heather, Stansfield, Kirstie H., Rousset, Olivier, Bibat, Genila, Yablonski, Mary E., Johnston, Michael V., Gjedde, Albert, Naidu, SakkuBai
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-09-2018
Subjects:
Autoradiography
Binding potential
Gene mutation
Intellectual disability
Neurotransmitter
Nigrostriatal pathway
Partial volume correction
Positron emission tomography
Postmortem
Radioligand
Autoradiography
Binding potential
Intellectual disability
Gene mutation
Postmortem
Neurotransmitter
Partial volume correction
Radioligand
Positron emission tomography
Nigrostriatal pathway
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Summary: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 D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2R density in the striatum of women with RTT compared to control subjects. 2) PET imaging of mouse striatum similarly demonstrated significant reductions in D2R density of 7–10 week-old hemizygous (Mecp2-null) and heterozygous (HET) mice compared to wild type (WT) mice. With age, the density of D2R declined in WT mice but not HET mice. 3) In contrast, postmortem autoradiography revealed no group differences in the density of D1R and D2R 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 D2R more likely explain the impaired ambulation and progressive rigidity observed rather than alterations in DAT. •PET imaging of dopamine function was performed in MeCP2-deficient humans and mice.•D2 receptor binding is reduced in Rett syndrome and in Mecp2-deficient mice.•Dopamine transporters are less affected than D2 receptors by MeCP2 deficiency.•Mecp2-deficient mice model dopamine dysfunction in Rett Syndrome•D2 receptors may play a role in motor deficits in Rett Syndrome.
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ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2018.05.019