title: GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact.
abstract: Alterations in the balance between excitatory and inhibitory neurotransmission have been implicated in several neurodevelopmental disorders. Neurofibromatosis type 1 is one of the most common monogenic disorders causing cognitive deficits for which studies on a mouse model (Nfl(+/-)) proposed increased γ-aminobutyric acid-mediated inhibitory neurotransmission as the neural mechanism underlying these deficits. To test whether a similar mechanism translates to the human disorder, we used magnetic resonance spectroscopy to measure γ-aminobutyric acid levels in the visual cortex of children and adolescents with neurofibromatosis type 1 (n = 20) and matched control subjects (n = 26). We found that patients with neurofibromatosis type 1 have significantly lower γ-aminobutyric acid levels than control subjects, and that neurofibromatosis type 1 mutation type significantly predicted cortical γ-aminobutyric acid. Moreover, functional imaging of the visual cortex indicated that blood oxygen level-dependent signal was correlated with γ-aminobutyric acid levels both in patients and control subjects. Our results provide in vivo evidence of γ-aminobutyric acidergic dysfunction in neurofibromatosis type 1 by showing a reduction in γ-aminobutyric acid levels in human patients. This finding is relevant to understand the physiological profile of the disorder and has implications for the identification of targets for therapeutic strategies.
authors: IBILI, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors: Inês R
authors: IR
authors: Violante
authors: Maria J
authors: MJ
authors: Ribeiro
authors: Richard A E
authors: RA
authors: Edden
authors: Pedro
authors: P
authors: Guimarães
authors: Inês
authors: I
authors: Bernardino
authors: José
authors: J
authors: Rebola
authors: Gil
authors: G
authors: Cunha
authors: Eduardo
authors: E
authors: Silva
authors: Miguel
authors: M
authors: Castelo-Branco
mesh_terms: D000293:Adolescent; D001923:Brain Chemistry; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D014793:Visual Cortex / Q000737:chemistry*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
chemical_list: D005680:gamma-Aminobutyric Acid