In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker

Abstract Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the Fragile X Mental Retardation (FMR1) gene. The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) whi...

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Autores principales:	Maria Mody, Yoann Petibon, Paul Han, Darshini Kuruppu, Chao Ma, Daniel Yokell, Ramesh Neelamegam, Marc D. Normandin, Georges El Fakhri, Anna-Liisa Brownell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c0ce7b7ae80f45c585088156fbb40608
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spelling	oai:doaj.org-article:c0ce7b7ae80f45c585088156fbb406082021-12-02T14:53:49ZIn vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker10.1038/s41598-021-94967-y2045-2322https://doaj.org/article/c0ce7b7ae80f45c585088156fbb406082021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94967-yhttps://doaj.org/toc/2045-2322Abstract Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the Fragile X Mental Retardation (FMR1) gene. The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) which has been implicated in the pathogenesis of the disorder. In the present study we used the radioligand 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB) in simultaneous PET-MR imaging of males with FXS and age- and gender-matched controls to assess the availability of mGlu5 receptors in relevant brain areas. Patients with FXS showed lower [18F]FPEB binding potential (p < 0.01), reflecting reduced mGluR5 availability, than the healthy controls throughout the brain, with significant group differences in insula, anterior cingulate, parahippocampal, inferior temporal and olfactory cortices, regions associated with deficits in inhibition, memory, and visuospatial processes characteristic of the disorder. The results are among the first to provide in vivo evidence of decreased availability of mGluR5 in the brain in individuals with FXS than in healthy controls. The consistent results across the subjects, despite the tremendous challenges with neuroimaging this population, highlight the robustness of the protocol and support for its use in drug occupancy studies; extending our radiotracer development and application efforts from mice to humans.Maria ModyYoann PetibonPaul HanDarshini KuruppuChao MaDaniel YokellRamesh NeelamegamMarc D. NormandinGeorges El FakhriAnna-Liisa BrownellNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Mody Yoann Petibon Paul Han Darshini Kuruppu Chao Ma Daniel Yokell Ramesh Neelamegam Marc D. Normandin Georges El Fakhri Anna-Liisa Brownell In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
description	Abstract Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the Fragile X Mental Retardation (FMR1) gene. The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) which has been implicated in the pathogenesis of the disorder. In the present study we used the radioligand 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB) in simultaneous PET-MR imaging of males with FXS and age- and gender-matched controls to assess the availability of mGlu5 receptors in relevant brain areas. Patients with FXS showed lower [18F]FPEB binding potential (p < 0.01), reflecting reduced mGluR5 availability, than the healthy controls throughout the brain, with significant group differences in insula, anterior cingulate, parahippocampal, inferior temporal and olfactory cortices, regions associated with deficits in inhibition, memory, and visuospatial processes characteristic of the disorder. The results are among the first to provide in vivo evidence of decreased availability of mGluR5 in the brain in individuals with FXS than in healthy controls. The consistent results across the subjects, despite the tremendous challenges with neuroimaging this population, highlight the robustness of the protocol and support for its use in drug occupancy studies; extending our radiotracer development and application efforts from mice to humans.
format	article
author	Maria Mody Yoann Petibon Paul Han Darshini Kuruppu Chao Ma Daniel Yokell Ramesh Neelamegam Marc D. Normandin Georges El Fakhri Anna-Liisa Brownell
author_facet	Maria Mody Yoann Petibon Paul Han Darshini Kuruppu Chao Ma Daniel Yokell Ramesh Neelamegam Marc D. Normandin Georges El Fakhri Anna-Liisa Brownell
author_sort	Maria Mody
title	In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
title_short	In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
title_full	In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
title_fullStr	In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
title_full_unstemmed	In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
title_sort	in vivo imaging of mglu5 receptor expression in humans with fragile x syndrome towards development of a potential biomarker
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c0ce7b7ae80f45c585088156fbb40608
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In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker

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