Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms22062863
Keywords
binding potential; cortex; caudate nucleus; cingulate; fragile X mental retardation 1 gene (FMR1); neurodevelopmental disorders; positron emission tomography (PET); putamen; radiotracer; thalamus
Funding
- Johns Hopkins University School of Medicine, Baltimore, Maryland
- Intellectual & Developmental Disabilities Research Center [U54 HD079123]
- Kennedy Krieger Institute
- Johns Hopkins Medical Institutions, Baltimore, Maryland
- National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [UL1 TR003098]
- NIH Roadmap for Medical Research
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Research suggests that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR(5)) plays a role in the pathogenesis of autism spectrum disorder (ASD). Contradictory findings about mGluR(5) expression in different subtypes of ASD have been reported. A study using a novel PET ligand found increased mGluR(5) expression in the cortical regions of participants with IASD, and reduced expression in all regions of men with FXS. This protocol shows promise as a valuable tool for measuring mGluR(5) expression in clinical trials for individuals with ASD and FXS.
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-[F-18]fluoro-5-(2-pyridinylethynyl)benzonitrile ([F-18]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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