Resveratrol Modulates and Reverses the Age-Related Effect on Adenosine-Mediated Signalling in SAMP8 Mice

Mol Neurobiol. 2019 Apr;56(4):2881-2895. doi: 10.1007/s12035-018-1281-8. Epub 2018 Aug 1.

Abstract

Resveratrol (RSV) is a natural compound present in berries, grapes and red wine that has shown some neuroprotective properties, but the mechanism by which RSV exhibits its protective role is not very well understood yet. Little is known about the effect of RSV on adenosinergic system, a system regulated in an age-dependent manner in SAMP8 mice, widely considered as an Alzheimer's model. Therefore, the aim of the present work was to assess whether RSV intake was able to modulate the adenosine-mediated signalling in SAMP8 mice. Data showed herein clearly demonstrate the ability of RSV to modulate adenosine receptor gene expression as well as transduction pathway mediated by receptors expressed on plasma membrane. Interestingly, this polyphenol was able to reverse the age-related loss of adenosine A1 receptors and its corresponding signalling pathway. Moreover, adenosine A2A receptors were not modulated by aging or RSV, but A2A-mediated signalling was completely desensitized after RSV treatment compared to untreated mice. Enzymes involved on adenosine metabolism, such as 5'-nucleotidase and adenosine deaminase, were found to be reduced after RSV treatment, but adenosine levels remained unchanged. Nevertheless, an age-related decrease on 5'-nucleotidase activity and adenosine and related metabolite levels was observed. In conclusion, our data show that RSV modulates adenosine-mediated signalling, strongly suggesting that the role of RSV via adenosine receptor signalling and its modulation of neurotransmission in neurodegenerative diseases should be considered as new therapeutic target for RSV neuroprotective effect.

Keywords: Adenosine signalling; Aging; Alzheimer’s disease; Resveratrol; SAMP8 mice.

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Adenosine / pharmacology*
  • Adenosine Deaminase / metabolism
  • Adenylyl Cyclases / metabolism
  • Aging / metabolism*
  • Animals
  • Cell Membrane / metabolism
  • Gene Expression Regulation / drug effects
  • Male
  • Metabolome
  • Mice
  • Receptors, Purinergic P1 / genetics
  • Receptors, Purinergic P1 / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction* / drug effects
  • Weight Gain / drug effects

Substances

  • Receptors, Purinergic P1
  • 5'-Nucleotidase
  • Adenosine Deaminase
  • Adenylyl Cyclases
  • Adenosine
  • Resveratrol