Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor–β Involvement

Abstract

Abstract. Genistein is a naturally occurring plant-derived phytoestrogen, present in the human diet, known to possess some beneficial effects. The present study investigated the effect of genistein on neuroprotection evaluated through electroencephalographic and behavioural correlates in a model of global cerebral ischemia in gerbils. Over the dose range tested, genistein (3 and 10 mg/ kg), given 5 min after recirculation antagonized the ischemia-induced electroencephalographic total spectral power decrease 7 days after ischemia; fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia; reversed ischemia-induced memory impairment evaluated through both nest building behaviour and object recognition test; decreased malondialdehyde overproduction in the brain, evaluated 7 days after reperfusion; and fully promoted the survival of pyramidal cells in the CA 1 hippocampal subfield. The selective antagonist for estrogen receptor-β (ERβ), 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) given 30 min before carotid occlusion, fully prevented the neuroprotective effect of genistein at the dose of 3 mg/kg. These results demonstrate the neuroprotective effect of genistein through the activation of ERβ and provide further grounds for the growing interest concerning the true potential of phytoestrogens as compounds to beneficially affect brain injury without having the disadvantages of estrogens.

Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring

“…In contrast to its detrimental effects on reproduction, previous studies have also focused on the benefits of GEN on brain function in various adult animal models such as Alzheimer's disease [17,18], global cerebral ischemia [19], and ovariectomy [20,21]. However, only a few studies have examined the effects of GEN on learning and memory in rat pups [22].…”

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

“…These findings indicate that both doses of GEN improved spatial learning and memory over time, when in a higher blood glucose state. It has been reported that GEN has ameliorating effects on brain function, in a number of disease models and in OVX rats [5][6][7][8][9]23]. The data reported here suggest that GEN is underworked when the body is in a normal state, but might lead to improved spatial learning and memory when homeostasis is lost.…”

“…A number of studies have shown that GEN has a neuroprotective or memory-improving effect in animal models of Alzheimer's disease [5] and global cerebral ischemia [6] and in ovariectomised (OVX) rats [7][8][9]. However, few studies have discussed the effects of GEN on learning and memory in the normal state.…”

Effect of carbaryl on some biochemical changes in PC12 cells: the protective effect of soy isoflavone genistein, and daidzein, and their mixed solution

“…It is believed that SIF, such as daidzein (DAI) and genistein (GEN), has an important role in potential health benefits . GEN is neuroprotective in an in vivo model of global cerebral ischemia in gerbils (Donzelli et al, 2010). In addition, the other main SIF, DAI, showed the same effects, protecting embryonic rat primary cortical neurons from ischemic-like injury in vitro and reducing ischemia/reperfusion-induced myocardial damage in vivo (Schreihofer & Redmond, 2009).…”