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

Brain Sciences

Danna Jennings¹  DavidS. Russell¹  Olivier Barret¹  JohnP. Seibyl¹  DejanB. Budimirovic²  Keith Slifer²  ElizabethM. Berry-Kravis³  Zabecca Brinson⁴  Thomas Sedlak⁴  Pankhuri Vyas⁴  JamesR. Brašić⁴  Ayon Nandi⁴  SamuelD. Martin⁴  DeanF. Wong⁴  Anil Mathur⁴ 

[1] Clinical Research, Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA;Department of Psychiatry and Behavioral Sciences-Child Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;Departments of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA;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;

关键词: binding potential;    caudate nucleus;    FMR1 gene;    Fragile X Mental Retardation Protein (FMRP);    genetic mutation;    magnetic resonance imaging (MRI);   

DOI  :  10.3390/brainsci10120899

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown