|
Title
|
|
|
|
Positron emission tomography (PET) quantification of receptors in the brain of fragile X patients
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Over the last several years, evidence has accumulated that the GABA(A) receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABA(A) receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABA(A) receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [C-11] flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABA(A) receptors. We measured regional GABA(A) receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABA(A) receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABA(A) receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABA(A) receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABA(A) receptor is a potential target for rational pharmacological treatment of fragile X syndrome. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
PLoS ONE
| |
|
Publication
|
|
|
|
2015
| |
|
ISSN
|
|
|
|
1932-6203
| |
|
DOI
|
|
|
|
10.1371/JOURNAL.PONE.0131486
| |
|
Volume/pages
|
|
|
|
10
:7
(2015)
, 12 p.
| |
|
Article Reference
|
|
|
|
e0131486
| |
|
ISI
|
|
|
|
000358836800015
| |
|
Pubmed ID
|
|
|
|
26222316
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|