Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs?

Environ Toxicol Pharmacol. 2014 May;37(3):916-27. doi: 10.1016/j.etap.2014.02.019. Epub 2014 Mar 3.

Abstract

Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChRα7, α4 and β2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin+ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin+ascorbic acid group (p < 0.05). While 8-hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChRα7 expressions were significantly increased in the aspirin+ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin+ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process.

Keywords: Acetylsalicylic acid; Ageing; NMDARs; Spatial memory; nAChRs.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Aspirin / pharmacology*
  • Behavior, Animal / drug effects
  • Cognition / drug effects*
  • Cognition / physiology
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Drug Combinations
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Memory / drug effects
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, Nicotinic / metabolism*

Substances

  • Antioxidants
  • Drug Combinations
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • ascorbic acid, aspirin drug combination
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Ascorbic Acid
  • Aspirin
  • N-methyl D-aspartate receptor subtype 2A