Age-related change of GLP-1R expression in rats can be detected by [ 18 F]AlF-NOTA-MAL-Cys 39-exendin-4

Brain Res. 2018 Nov 1;1698:213-219. doi: 10.1016/j.brainres.2018.08.022. Epub 2018 Aug 23.

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) has been demonstrated as a potential therapeutic target for some neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. Besides, its distribution and density in brain regions are closely associated with cognition, motor function, learning and memory. Given the relationship between age and these neurological diseases, we firstly examined the influences of age on GLP-1R expression using [18F]AlF-NOTA-MAL-Cys39-exendin-4 microPET imaging. The image showed that GLP-1R expression in nearly all regions of the brain of aged rats was evidently lower than that of normal rats. Significant differences were found in olfactory, striatum, hypothalamus, substantial nigra, and hippocampus, which have inseparable relations with some mental and neurological diseases such as PD and AD. Data obtained from biodistribution and immunohistochemistry staining also confirmed the image results. Taken together, these results illustrated decreased expression of GLP-1R in the brain of aged rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4, which implied GLP-1R as a reliable target and GLP-1R PET imaging could be a promising technology in the field of neurological diseases.

Keywords: Age effects; Exendin-4; Glucagon-like peptide-1 receptor (GLP-1R); Neurological diseases; PET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Cysteine / analogs & derivatives
  • Exenatide / metabolism
  • Female
  • Fluorine Radioisotopes
  • Glucagon-Like Peptide-1 Receptor / biosynthesis*
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Heterocyclic Compounds, 1-Ring
  • Male
  • Maleimides
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / metabolism
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Heterocyclic Compounds, 1-Ring
  • Maleimides
  • Radiopharmaceuticals
  • Receptors, Glucagon
  • S-(bismaleimidoethyl ether)cysteine
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Exenatide
  • Cysteine