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

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 2012

Fingerprint

Vesicular Acetylcholine Transport Proteins
Rett Syndrome
Activities of Daily Living
Binding Sites
Corpus Striatum
Single-Photon Emission-Computed Tomography
Brain
Methyl-CpG-Binding Protein 2
X Chromosome Inactivation
Intravenous Injections
Cerebellum
Healthy Volunteers
Mutation

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome. / Brašić, James Robert; Bibat, Genila; Kumar, Anil; Zhou, Yun; Hilton, John; Yablonski, Marybeth E.; Dogan, Ahmet Semih; Guevara, Maria Rita; Stephane, Massoud; Johnston, Michael; Wong, Dean Foster; Naidu, Sakkubai.

In: Synapse, Vol. 66, No. 6, 06.2012, p. 471-482.

Research output: Contribution to journalArticle

Brašić, James Robert; Bibat, Genila; Kumar, Anil; Zhou, Yun; Hilton, John; Yablonski, Marybeth E.; Dogan, Ahmet Semih; Guevara, Maria Rita; Stephane, Massoud; Johnston, Michael; Wong, Dean Foster; Naidu, Sakkubai / Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome.

In: Synapse, Vol. 66, No. 6, 06.2012, p. 471-482.

Research output: Contribution to journalArticle

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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; 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.",
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