Aβ pathology downregulates brain mGluR5 density in a mouse model of Alzheimer

Neuropharmacology. 2018 May 1:133:512-517. doi: 10.1016/j.neuropharm.2018.02.003. Epub 2018 Feb 7.

Abstract

The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([18F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniques. The non-displaceable binding potential values for mGluR5 was estimated by the Logan's graphical analysis. Brain PET imaging revealed that radioactivities in the hippocampus and the striatum were significantly lower in 5xFAD mice compared to control animals. Binding values were also significantly lowered in 5xFAD mice. This decline was validated by immunoblotting of protein isolates from brain tissues, as the mean band density for 5xFAD mice had a lower mGluR5 intensity than for wild type mice. These results indicated that mGluR5 levels in 5xFAD mice were down regulated in the limbic system.

Keywords: 5xFAD mice; Alzheimer's disease; PET; [(18)F]FPEB; mGluR5; β-Amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics*
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Nitriles / pharmacokinetics
  • Peptide Fragments / metabolism
  • Positron-Emission Tomography
  • Presenilin-1 / genetics
  • Pyridines / pharmacokinetics
  • Receptor, Metabotropic Glutamate 5 / metabolism*

Substances

  • 3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile
  • Amyloid
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Nitriles
  • Peptide Fragments
  • Presenilin-1
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • amyloid beta-protein (1-42)