Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with Rett syndrome.
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) [¹²³ I]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.
The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Maryland 21287-0807, USA. brasic@jhmi.edu
James Robert
JR
Brašić
Genila
G
Bibat
Anil
A
Kumar
Yun
Y
Zhou
John
J
Hilton
Marybeth E
ME
Yablonski
Ahmet Semih
AS
Dogan
Maria Rita
MR
Guevara
Massoud
M
Stephane
Michael
M
Johnston
Dean Foster
DF
Wong
Sakkubai
S
Naidu
D000203:Activities of Daily Living; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010880:Piperidines; D015518:Rett Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics; D013764:Tetrahydronaphthalenes; D015899:Tomography, Emission-Computed, Single-Photon; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism*
D051783:Methyl-CpG-Binding Protein 2; D010880:Piperidines; D013764:Tetrahydronaphthalenes; D050494:Vesicular Acetylcholine Transport Proteins; C065043:5-iodobenzovesamicol