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

Autor: Ayon Nandi, Dean F. Wong, Pankhuri Vyas, Elizabeth Berry-Kravis, Dejan B. Budimirovic, Anil Mathur, Samuel D. Martin, Zabecca Brinson, John Seibyl, Olivier Barret, Keith J. Slifer, James Robert Brašić, Danna Jennings, Thomas W. Sedlak, David S. Russell
Rok vydání: 2020
Předmět:
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
animal structures
FMR1 gene
magnetic resonance imaging (MRI)
Receptor expression
animal diseases
Caudate nucleus
3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB)
Article
lcsh:RC321-571
Glutamatergic
Internal medicine
mental disorders
medicine
positron emission tomography (PET)
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Metabotropic glutamate receptor 5
business.industry
musculoskeletal
neural
and ocular physiology
General Neuroscience
binding potential
caudate nucleus
Binding potential
medicine.disease
FMR1
neuropsychological testing
Fragile X syndrome
Endocrinology
mosaicism
nervous system
Metabotropic glutamate receptor
genetic mutation
business
Fragile X Mental Retardation Protein (FMRP)
Zdroj: Brain Sciences
Volume 10
Issue 12
Brain Sciences, Vol 10, Iss 899, p 899 (2020)
ISSN: 2076-3425
Popis: 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.
Databáze: OpenAIRE
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