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Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study
Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR(5)) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR(5) expression provide conflicting findings about the nature of dysregulatio...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999711/ https://www.ncbi.nlm.nih.gov/pubmed/33799851 http://dx.doi.org/10.3390/ijms22062863 |
Sumario: | Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR(5)) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR(5) expression provide conflicting findings about the nature of dysregulation of cerebral mGluR(5) pathways in subtypes of ASD. The demonstration of reduced mGluR(5) expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR(5) expression in ASD. We aimed to (A) compare and contrast mGluR(5) expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[(18)F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([(18)F]FPEB), a novel, specific mGluR(5) PET ligand to quantitatively measure the density and the distribution of mGluR(5)s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR(5) expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR(5) expression in clinical trials of individuals with IASD and FXS and related conditions. |
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