Stimulatory Effects of (+)-Epicatechin on Short- and Long-Term Memory in Aged Rats: Underlying Mechanisms.

Background/Objectives: We previously reported that the flavanol (+)-epicatechin (+Epi) enhances adult mice short-term working memory and neurogenesis. This study aimed to characterize the effects of +Epi on short- and long-term memory, to modulate mitochondria structure/function, oxidative stress (OS) and inflammation associated cytokines in the hippocampus and pre-frontal cortex of aged rats. Methods: Experiments were conducted using aged (23 month old) male Sprague Dawley rats. The control group (n = 6/group) were exposed to vehicle (water) only while the treated group, was provided +Epi at 1 mg/kg/day by oral gavage for 8 weeks. Open-field recognition tests were used to evaluate short- and long-term memory. The hippocampus and frontal cortex were sampled and citrate synthase activity, ATP levels, mitochondrial proteins, cytokines (IL-1β, IL-6, TNF-a and IL-11), protein carbonylation, lipid peroxidation (malonaldehyde; MDA), superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx) and catalase activity were quantified. Results: There was a significant improvement in both short- and long-term memory in the +Epi treated group vs. controls. Mitochondrial bioenergetics also improved with treatment as determined by increased citrate synthase activity and ATP content. Relative levels of the mitochondrial proteins mitofilin and complex V increased with +Epi. +Epi suppressed protein carbonyls and MDA levels. OS buffering systems were significantly enhanced with +Epi as per increases in SOD2, GPx and catalase enzyme activities. +Epi also decreased pro-inflammatory and stimulated anti-inflammatory cytokines vs. controls. Conclusions: Results demonstrate +Epi improves mitochondrial function, reduces OS and inflammation in the hippocampus and cortex leading to improved short- and long-term memory in aged animals providing evidence for possible mechanisms of action.