Prader-Willi syndrome (PWS) is a multi-system disorder characterized clinically by abnormal mental and physical development. PWS patients have a deletion in an imprinted region on paternal chromosome 15 (15q11-13), maternal disomy for this segment, or rarely, a chromosomal imprinting center deletion that gives rise to suppression of the equivalent paternal genes. Within the affected segment of chromosome 15 are genes encoding the α5, β3 and γ3 subunits of the gamma-aminobutyric acid type-A (GABAA) receptor. Therefore, altered neurobehavioral function could arise in PWS due directly to altered GABAA receptor composition and expression, or alternatively, from brain developmental and maturational effects of these or other genes in the imprinted region. The aim of the present study was to assess cerebral GABAA receptors in PWS with the use of positron emission tomography of the benzodiazepine binding site employing [11C]flumazenil ([11C]FMZ). A reduction in [11C]FMZ binding was found predominantly in the cingulate, frontal and temporal neocortices and insula in six adult PWS patients compared to nine normal subjects. A possible role for the deleted β3 subunit gene in PWS is supported in part by the wide cortical distribution of its mRNA expression and the effects of experimental knockouts on benzodiazepine binding described in prior studies. Altered GABAA receptor composition or number in these cortical regions may account for neurobehavioral abnormalities in PWS including mild mental retardation, poor impulse control, and impaired responses to somatic pain.
GABA A receptor abnormalities in Prader-Willi syndrome assessed with positron emission tomography and [11C]flumazenil / G. Lucignani, A. Panzacchi, L. Bosio, R.M. Moresco, L. Ravasi, I. Coppa, G. Chiumello, K. Frey, R. Koeppe, F. Fazio. - In: NEUROIMAGE. - ISSN 1053-8119. - 22:1(2004), pp. 22-28.
|Titolo:||GABA A receptor abnormalities in Prader-Willi syndrome assessed with positron emission tomography and [11C]flumazenil|
LUCIGNANI, GIOVANNI (Primo)
|Parole Chiave:||Benzodiazepine; Genes; Prader-Willi syndrome|
|Settore Scientifico Disciplinare:||Settore MED/36 - Diagnostica per Immagini e Radioterapia|
|Data di pubblicazione:||2004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neuroimage.2003.10.050|
|Appare nelle tipologie:||01 - Articolo su periodico|