Grape Seed Proanthocyanidin and Swimming Exercise Protects Against Cognitive Decline: A Study on M1 Acetylcholine Receptors in Aging Male Rat Brain

Neurochem Res. 2017 Dec;42(12):3573-3586. doi: 10.1007/s11064-017-2406-6. Epub 2017 Oct 9.


Decline in cognition is one of the earliest signs of normal brain aging. Several dietary and non-pharmacological approaches have been tested to slow down this process. The aim of the present study was to assess the influence of grape seed proanthocyanidin extract (GSPE) either individually or in combination with swimming training on acetylcholine esterase activity (AChE) and m1 acetylcholine receptor (m1AChR) on the extent of cognitive decline with aging. The experimental protocol included the oral administration of GSPE (400 mg/kg body weight) for 14 weeks to 4 (adult) and 18-month-old (middle-aged) male Wistar rats along with swimming training. They were subjected to behavioral testing followed by biochemical and immunohistochemical analysis. The results demonstrated that GSPE supplementation and swimming training either individually or in combination had an improvement on acquisition and working memory with reduced AChE activity in the medial prefrontal cortex (mPFC) and hippocampus (HC). Immunohistochemical and qRT-PCR evaluation showed an increase in m1AChR protein and mRNA in the CA1 region of HC and also mPFC upon swimming training with GSPE treatment. These beneficial and synergistic effects of GSPE and swimming training are suggestive as interventions in modulating the cognitive function, with GSPE alone being more suitable for middle-aged individuals.

Keywords: Aging; Brain; Exercise; GSPE; Muscarinic acetylcholine receptor.

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidants / pharmacology
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Grape Seed Extract / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Physical Conditioning, Animal
  • Proanthocyanidins / pharmacology*
  • Protective Agents / pharmacology
  • Rats, Wistar
  • Receptors, Cholinergic / metabolism*


  • Antioxidants
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Proanthocyanidins
  • Protective Agents
  • Receptors, Cholinergic
  • proanthocyanidin