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

Authors

  • James Robert Brašić,

    Corresponding author
    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    • Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Section of High Resolution Brain Positron Emission Tomography Imaging, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, 601 North Caroline Street, Room 3245, Baltimore, MD 21287-0807, USA
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  • Genila Bibat,

    1. Department of Pediatrics, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    2. Neurogenetics Unit, Kennedy Krieger Institute, Baltimore, Maryland 21205
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  • Anil Kumar,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • Yun Zhou,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • John Hilton,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • Marybeth E. Yablonski,

    1. Neurogenetics Unit, Kennedy Krieger Institute, Baltimore, Maryland 21205
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  • Ahmet Semih Dogan,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • Maria Rita Guevara,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • Massoud Stephane,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
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  • Michael Johnston,

    1. Department of Pediatrics, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    2. Department of Neurology, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    3. Department of Physical Medicine and Rehabilitation, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    4. Neuroscience Laboratory, Kennedy Krieger Institute, Baltimore, Maryland 21205
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  • Dean Foster Wong,

    1. Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    2. The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Wood Basic Science Building, Baltimore, Maryland 21205
    3. Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Meyer Building, Baltimore, Maryland 21287
    4. Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205
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  • Sakkubai Naidu

    1. Department of Pediatrics, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    2. Neurogenetics Unit, Kennedy Krieger Institute, Baltimore, Maryland 21205
    3. Department of Neurology, The Johns Hopkins University School of Medicine, Johns Hopkins Outpatient Center, Baltimore, Maryland 21287-0807
    4. Neurology Laboratory, Kennedy Krieger Institute, Baltimore, Maryland 21205
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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; R2 = 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. Synapse, 2012. © 2011 Wiley Periodicals, Inc.

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