Dietary genistein and 17β-estradiol implants differentially influence locomotor and cognitive functions following transient focal ischemia in middle-aged ovariectomized rats at different lengths of estrogen deprivation

Genistein possesses estrogenic activity and has been considered a potential replacement for estrogen replacement therapy after menopause. In the current study, we investigated the neuroprotective effects of dietary genistein at varied lengths of estrogen deprivation in middle-aged ovariectomized Sprague-Dawley rats under ischemic conditions. Two weeks of treatment with dietary genistein at 42 mg/kg but not 17β-estradiol implants improved cognitive flexibility (Morris water maze test) after short-term estrogen deprivation (2 weeks) but not long-term estrogen deprivation (12 weeks). 17β-estradiol implants but not dietary genistein improved locomotor asymmetry (cylinder test) after long-term but not short-term estrogen deprivation. Dietary genistein but not 17β-estradiol implant improved early phase motor learning (rotarod test) after long-term estrogen deprivation. Neither 17β-estradiol implant nor dietary genistein reduced infarct size after either short-term or long-term estrogen deprivation. Genistein, however, reduced ionized calcium-binding adaptor molecule-1 (Iba1) expression, a marker of brain inflammation, at the ipsilateral side of stroke injury after short-term but not long-term estrogen deprivation. This study suggests that the neuroprotective effects of dietary genistein on motor and cognitive functions are distinctly influenced by the length of estrogen deprivation following focal ischemia. Significance: There is an increasing postmenopausal population opting for homeopathic medicines for the management of menopausal symptoms due to the perceived distrust in estrogen use as hormone replacement. Basic and clinical studies support the notion that early, but not delayed, hormone replacement after menopause is beneficial. Furthermore, evidence suggests that delaying hormone replacement augments the detrimental, rather than the beneficial effects of estrogens. Because of the active consideration of soy isoflavones including genistein as alternatives to estrogen replacement, it is necessary to understand the ramifications of soy isoflavones use when their administration is begun at various times after menopause.