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Updated: Mar 17, 2026
Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
GABA deficiency in NF1: A multimodal [11C]-flumazenil and spectroscopy study
Inês R Violante1, Miguel Patricio2, Inês Bernardino2
1From the Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine (I.R.V., M.P., I.B., J.R., M.C.-B.), Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine (M.P., M.C.-B.), and Institute of Nuclear Sciences Applied to Health (A.J.A., N.F., M.C.-B.), University of Coimbra, Portugal; and Division of Brain Sciences (I.R.V.), Department of Medicine, Hammersmith Hospital Campus, Imperial College London, UK. i.violante@imperial.ac.uk.
Objective:
To provide a comprehensive investigation of the γ-aminobutyric acid (GABA) system in patients with neurofibromatosis type 1 (NF1) that allows understanding the nature of the GABA imbalance in humans at pre- and postsynaptic levels.
Methods:
In this cross-sectional study, we employed multimodal imaging and spectroscopy measures to investigate GABA type A (GABAA) receptor binding, using [(11)C]-flumazenil PET, and GABA concentration, using magnetic resonance spectroscopy (MRS). Fourteen adult patients with NF1 and 13 matched controls were included in the study. MRS was performed in the occipital cortex and in a frontal region centered in the functionally localized frontal eye fields. PET and MRS acquisitions were performed in the same day.
Results:
Patients with NF1 have reduced concentration of GABA+ in the occipital cortex (p = 0.004) and frontal eye fields (p = 0.026). PET results showed decreased binding of GABAA receptors in patients in the parieto-occipital cortex, midbrain, and thalamus, which are not explained by decreased gray matter levels.
Conclusions:
Abnormalities in the GABA system in NF1 involve both GABA concentration and GABAA receptor density suggestive of neurodevelopmental synaptopathy with both pre- and postsynaptic involvement.
