Combination of N-acetylcysteine, α-lipoic acid and α-tocopherol substantially prevents the brain synaptosomal alterations and memory and learning deficits of aged rats

Exp Gerontol. 2014 Feb:50:19-25. doi: 10.1016/j.exger.2013.11.008. Epub 2013 Nov 27.


This study has compared several synaptosomal parameters in three groups of rats: young (46 months), aged (22-24 months) and antioxidant supplemented aged rats (antioxidant supplementation given with the diet as a combination of N-acetylcysteine, α-lipoic acid and α-tocopherol from 18 months onwards till 22-24 months). The synaptosomes from aged rat brain, in comparison to those of young animals, exhibit an increased membrane potential with altered contents of Na(+) and K(+) under basal incubation condition and in the presence of depolarizing agents. The intrasynaptosomal Ca(2+) is also higher in aged than in young rat. These age-dependent changes in synaptosomal parameters are prevented markedly in the antioxidant supplemented group. When examined on T-maze, the aged animals are noticeably impaired in learning and memory functions, but the deficit is remarkably prevented in the antioxidant supplemented aged animals. It is suggested that the synaptosomal alterations partly contribute to the cognitive deficits of aged animals, and both are rescued by long-term antioxidant supplementation.

Keywords: Antioxidant; Brain aging; Cognitive deficit; Ion channel; Membrane potential; Oxidative stress; Synaptosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use
  • Aging / metabolism
  • Aging / psychology
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Brain / drug effects*
  • Brain / metabolism
  • Calcium / metabolism
  • Dietary Supplements
  • Drug Evaluation, Preclinical / methods
  • Drug Therapy, Combination
  • Learning Disabilities / prevention & control*
  • Maze Learning / drug effects
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Memory Disorders / prevention & control*
  • Oxidative Stress / drug effects
  • Potassium / metabolism
  • Rats
  • Sodium / metabolism
  • Synaptosomes / drug effects*
  • Synaptosomes / metabolism
  • Thioctic Acid / pharmacology
  • Thioctic Acid / therapeutic use
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use


  • Antioxidants
  • Thioctic Acid
  • Sodium
  • alpha-Tocopherol
  • Potassium
  • Calcium
  • Acetylcysteine