The flavanol (−)‐epicatechin improves learning, memory and anxiety behavior in ovariectomized rats

Abstract

The loss of gonadal function in women during menopause is known to contribute to impaired memory and learning performance. Conversely, menopausal women using estrogen replacement therapy (ERT) can evidence improvements on these endpoints. However, the long-term use of ERT has been show to have important health risks such as increased rates for certain cancers. Supplements, such as phytoestrogens and/or flavonoids have emerged as potential alternative treatments during menopause that may offer safer options. (−)-Epicatechin (Epi), is the most abundant flavonoid present in cacao seeds. Epi is related with a number of healthy cardiometabolic effects in preclinical models and in humans. Such effects include improvements in vascular, cardiac and metabolic function, stimulation of mitochondrial biogenesis and upregulation of enzymatic and non-enzymatic antioxidant systems in tissues such as the heart and skeletal muscle. These effects appear to be related to the binding/stimulation of Epi to the G-protein estrogen receptor (GPER). However, the effects of Epi in postmenopausal female model neurological endpoints including learning, memory and anxiety are poorly understood. In this study we evaluated the effect of Epi (0.01 and 1 mg/kg body weight) on memory, learning and anxiety behavior of ovariectomized (Ovx) rats, an accepted animal model of menopause. For this purpose, Ovx rats were evaluated using two behavioral tests, 1) object recognition task (ORT) (involving short and long term memory; STM, LTM respectively) and, 2) T-maze (anxiety model). As shown in the figure, in the ORT, Ovx rats evidenced significant improvement in short and long term memory with 0.01 mg/Kg of Epi. For anxiety T-maze measures, Epi significantly reduced delayed avoidance latency markedly with the dose of 1.0 mg/Kg and escape latency with both doses of Epi. These data suggest that low dose of Epi improves the recognition memory in Ovx rats and can also reduce anxiety. The underlying mechanisms may be related to the positive effects of Epi on regulators/stimulators of mitochondrial biogenesis and oxidative stress buffering systems which we have reported to occur in senile animals. These results warrant the implementation of future studies in human subjects using Epi. Support or Funding Information DoD 150090 to FV This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.