Reduced Expression of Cerebral Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome

James R. Brašić; Ayon Nandi; David S. Russell; Danna Jennings; Olivier Barret; Anil Mathur; Keith Slifer; Thomas Sedlak; Samuel D. Martin; Zabecca Brinson; Pankhuri Vyas; John P. Seibyl; Elizabeth M. Berry-Kravis; Dean F. Wong; Dejan B. Budimirovic

doi:10.3390/brainsci10120899

Brain Sciences (Nov 2020)

Reduced Expression of Cerebral Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome

James R. Brašić,
Ayon Nandi,
David S. Russell,
Danna Jennings,
Olivier Barret,
Anil Mathur,
Keith Slifer,
Thomas Sedlak,
Samuel D. Martin,
Zabecca Brinson,
Pankhuri Vyas,
John P. Seibyl,
Elizabeth M. Berry-Kravis,
Dean F. Wong,
Dejan B. Budimirovic

Affiliations

James R. Brašić: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Ayon Nandi: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
David S. Russell: Clinical Research, Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA
Danna Jennings: Clinical Research, Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA
Olivier Barret: Clinical Research, Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA
Anil Mathur: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Keith Slifer: Department of Psychiatry and Behavioral Sciences-Child Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Thomas Sedlak: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Samuel D. Martin: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Zabecca Brinson: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Pankhuri Vyas: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
John P. Seibyl: Clinical Research, Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA
Elizabeth M. Berry-Kravis: Departments of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA
Dean F. Wong: Section of High Resolution Brain Positron Emission Tomography Imaging, Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Dejan B. Budimirovic: Department of Psychiatry and Behavioral Sciences-Child Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

DOI: https://doi.org/10.3390/brainsci10120899
Journal volume & issue: Vol. 10, no. 12
p. 899

Abstract

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Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) in fmr1 knockout (KO) mouse models have not been confirmed in humans with FXS. Measurement of cerebral mGluR5 expression in humans with FXS exposed to NAMs might help in that effort. We used positron emission tomography (PET) to measure the mGluR5 density as a proxy of mGluR5 expression in cortical and subcortical brain regions to confirm target engagement of NAMs for mGluR5s. The density and the distribution of mGluR5 were measured in two independent samples of men with FXS (N = 9) and typical development (TD) (N = 8). We showed the feasibility of this complex study including MRI and PET, meaning that this challenging protocol can be accomplished in men with FXS with an adequate preparation. Analysis of variance of estimated mGluR5 expression showed that mGluR5 expression was significantly reduced in cortical and subcortical regions of men with FXS in contrast to age-matched men with TD.

Published in Brain Sciences

ISSN: 2076-3425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.mdpi.com/journal/brainsci/

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