Abstract
Diminished estrogen influence at menopause is reported to be associated with cognitive decline, heightened anxiety and hypertension. While estrogen therapy is often prescribed to overcome these behavioral and physiological deficits, antioxidants which have been shown beneficial are gaining nutritional intervention and popularity. Therefore, in the present study, utilizing the antioxidant properties of grapes, we have examined effect of 3 weeks of grape powder (GP; 15 g/L dissolved in tap water) treatment on anxiety-like behavior, learning-memory impairment and high blood pressure in ovariectomized (OVX) rats. Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX and OVX+GP treated. We observed a significant increase in systolic and diastolic blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy increased anxiety-like behavior and caused learning and memory impairment in rats as compared to sham-controls. Interestingly, providing grape powder treated water to OVX rats restored both systolic and diastolic blood pressure, decreased anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited an impaired long term potentiation which was restored with grape powder treatment. Furthermore, ovariectomy increased oxidative stress in the brain, serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein expression in the hippocampus but not in the cortex and amygdala of OVX rats, while grape powder treatment reversed these effects. Other antioxidant enzyme levels, including manganese superoxide dismutase (SOD) and Cu/Zn SOD remained unchanged. We suggest that grape powder by regulating oxidative stress mechanisms exerts its protective effect on blood pressure, learning-memory and anxiety-like behavior. Our study is the first to examine behavioral, biochemical, physiological and electrophysiological outcome of estrogen depletion in rats and to test protective role of grape powder, all in the same study.
Highlights
It is well known that estrogen is critical for normal brain function; and its depletion at menopause accounts, at least in part, for the cognitive decline, anxiety and hypertension [1,2,3,4]
We provide evidence to suggest that estrogen depletion via ovariectomization increased anxiety-like behavior, caused memory impairment and increased blood pressure in female Wistar rats
Treatment of OVX rats with grape powder for 3 weeks was marked by improvement in anxiety-like behavior and learningmemory function, restoration of both systolic and diastolic blood pressure as well as reduction in oxidative stress
Summary
It is well known that estrogen is critical for normal brain function; and its depletion at menopause accounts, at least in part, for the cognitive decline, anxiety and hypertension [1,2,3,4]. Menopausal women, nearly 50 million in the United States alone, experience heightened anxiety, hypertension and memory impairment and often opt for estrogen replacement therapy [3,6]. While this therapy offers some relief, it carries with it the associated risks of breast cancer, heart disease and stroke [6]. Dietary supplementation of antioxidants is reported to protect menopausal and postmenopausal women against high levels of oxidative stress [11]. Low ratio is an indicator of oxidative stress in cells and tissues This is considered crucial for women of menopausal and postmenopausal age [15]. Use of herbal supplements, vitamins, minerals, antioxidants, and antidepressants is gaining attention [17,18,19,20,21]
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