Cerebral expression of metabotropic glutamate receptor subtype 5 in idiopathic autism spectrum disorder and fragile x syndrome: A pilot study

James Robert Brašić, Ayon Nandi, David S. Russell, Danna Jennings, Olivier Barret, Samuel D. Martin, Keith Slifer, Thomas Sedlak, John P. Seibyl, Dean F. Wong, Dejan B. Budimirovic

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in sub-types of ASD. The demonstration of reduced mGluR5 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 mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 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 ad-ministered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18 F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 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 mGluR5 expression in clinical trials of individuals with IASD and FXS and related condi-tions.

Original languageEnglish
Article number2863
Pages (from-to)1-16
Number of pages16
JournalInternational journal of molecular sciences
Volume22
Issue number6
DOIs
StatePublished - Mar 2 2021

Keywords

  • Binding potential
  • Caudate nucleus
  • Cingulate
  • Cortex
  • Fragile X mental retardation 1 gene (FMR1)
  • Neurodevelopmental disorders
  • Positron emission tomography (PET)
  • Putamen
  • Radiotracer
  • Thalamus

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