@article{a7f0352af34f4834bf712616b0534ace,
title = "Cerebral expression of metabotropic glutamate receptor subtype 5 in idiopathic autism spectrum disorder and fragile x syndrome: A pilot study",
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.",
keywords = "Binding potential, Caudate nucleus, Cingulate, Cortex, Fragile X mental retardation 1 gene (FMR1), Neurodevelopmental disorders, Positron emission tomography (PET), Putamen, Radiotracer, Thalamus",
author = "Bra{\v s}i{\'c}, {James Robert} and Ayon Nandi and Russell, {David S.} and Danna Jennings and Olivier Barret and Martin, {Samuel D.} and Keith Slifer and Thomas Sedlak and Seibyl, {John P.} and Wong, {Dean F.} and Budimirovic, {Dejan B.}",
note = "Funding Information: Acknowledgments: The authors thank the patients and families for their participation and dedication to these studies; they are the inspiration for our efforts at improving treatments. The authors thank the FORWARD Database and Registry of the National Fragile X Foundation (NFXF) funded by the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, for referral of participants. The authors thank the teams of the Institute of Neurodegenerative Disorders, the Positron Emission Tomography (PET) Radiotracer Service Center, and the Research Magnetic Resonance Imaging (MRI) Service Center of the Johns Hopkins University School of Medicine for conducting the scans. The authors thank Hiroto Kuwabara for PET analysis. The authors thank Brian Hwang for posing for the photograph by J.R.B. on the Graphical Abstract. Earlier versions of this article were presented at the 2020 Annual Meeting, Society of Nuclear Medicine and Molecular Imaging, 11–14 July 2020, the World Molecular Imaging Congress 2020, and the Society for Neuroscience Global Connectome, Virtual [43]. Funding Information: Funding: This research was made possible by a Radiology BRidge/Development Funding Initiative to STimulate and Advance Research (RAD BriteStar Bridge) Award from the Johns Hopkins University School of Medicine, Baltimore, Maryland to J.R.B. with the assistance of D.F.W.; the Intellectual & Developmental Disabilities Research Center (U54 HD079123), Kennedy Krieger Institute, and Johns Hopkins Medical Institutions, Baltimore, Maryland, to J.R.B.; and the Johns Hopkins Institute for Clinical and Translational Research (ICTR), Johns Hopkins University School of Medicine, Baltimore, Maryland, to J.R.B., which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. Funding Information: This research was made possible by a Radiology BRidge/Development Funding Initia-tive to STimulate and Advance Research (RAD BriteStar Bridge) Award from the Johns Hopkins University School of Medicine, Baltimore, Maryland to J.R.B. with the assistance of D.F.W.; the Intellectual & Developmental Disabilities Research Center (U54 HD079123), Kennedy Krieger In-stitute, and Johns Hopkins Medical Institutions, Baltimore, Maryland, to J.R.B.; and the Johns Hopkins Institute for Clinical and Translational Research (ICTR), Johns Hopkins University School of Medicine, Baltimore, Maryland, to J.R.B., which is funded in part by Grant Number UL1 TR003098 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR, NCATS, or NIH. Publisher Copyright: {\textcopyright} 2021 by the authors.",
year = "2021",
month = mar,
day = "2",
doi = "10.3390/ijms22062863",
language = "English (US)",
volume = "22",
pages = "1--16",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",
}