Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome

James Robert Brašić, Genila Bibat, Anil Kumar, Yun Zhou, John Hilton, Marybeth E. Yablonski, Ahmet Semih Dogan, Maria Rita Guevara, Massoud Stephane, Michael Johnston, Dean Foster Wong, Sakkubai Naidu

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    Rett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X-linked methyl-CpG-binding protein 2 located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is correlated with the density of vesicular acetylcholine transporters in the striata of women with RTT. The density of the vesicular acetylcholine transporters in the living human brain can be estimated by single-photon emission-computed tomography (SPECT) after the administration of (-)-5-[ 123I]iodobenzovesamicol ([ 123I]IBVM). Twenty-four hours following the intravenous injection of ∼333 MBq (9 mCi) [ 123I]IBVM, four women with RTT and nine healthy adult volunteer control participants underwent SPECT brain scans for 60 min. The Vesicular Acetylcholine Transporter Binding Site Index (Kuhl et al., 1994), a measurement of the density of vesicular acetylcholine transporters, was estimated in the striatum and the reference structure, the cerebellum. The women with RTT were assessed for certain ADL. Although the striatal Vesicular Acetylcholine Transporter Binding Site Index was not significantly lower in RTT (5.2 ± 0.9) than in healthy adults (5.7 ± 1.6), RTT striatal Vesicular Acetylcholine Transporter Binding Site Indices and ADL scores were linearly associated (ADL = 0.89*(Vesicular Acetylcholine Transporter Binding Site Index) + 4.5; R 2 = 0.93; P < 0.01), suggesting a correlation between the ability to perform ADL and the density of vesicular acetylcholine transporters in the striata of women with RTT. [ 123I]IBVM is a promising tool to characterize the pathophysiological mechanisms of RTT and other neurodevelopmental disabilities.

    Original languageEnglish (US)
    Pages (from-to)471-482
    Number of pages12
    JournalSynapse
    Volume66
    Issue number6
    DOIs
    StatePublished - Jun 1 2012

    Keywords

    • (-) isomer
    • 123I-labeled
    • 5-iodobenzovesamicol
    • Emission-computed
    • Single-photon
    • Tomography

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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  • Cite this

    Brašić, J. R., Bibat, G., Kumar, A., Zhou, Y., Hilton, J., Yablonski, M. E., Dogan, A. S., Guevara, M. R., Stephane, M., Johnston, M., Wong, D. F., & Naidu, S. (2012). Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome. Synapse, 66(6), 471-482. https://doi.org/10.1002/syn.21515