A high soy diet enhances neurotropin receptor and Bcl-XL gene expression in the brains of ovariectomized female rats

Abstract

Estrogen is a powerful neuroprotective agent with the ability to induce trophic and antiapoptotic genes. However, concerns about negative overall health consequences of estrogen replacement after menopause have led to the adoption of other strategies to obtain estrogen's benefits in the brain, including the use of selective estrogen receptor modulators, high soy diets, or isoflavone supplements. This study sought to determine the ability of a high soy diet to induce neuroprotective gene expression in the female rat brain and compare the actions of soy with estrogen. Adult ovariectomized female rats were treated with 3 days of high dose estrogen or 2 weeks of a soy-free diet, a high soy diet, or chronic low dose estrogen. Different brain regions were microdissected and subjected to real time RT-PCR for neuroprotective genes previously shown to be estrogen-regulated. The principle findings are that a high soy diet led to the widespread increase in the mRNA for neurotropin receptors TrkA and p75-NTR, and the antiapoptotic Bcl-2 family member Bcl-X(L). Immunohistochemistry confirmed increases in both TrkA and Bcl-X(L). Chronic low dose estrogen mimicked some of these effects, but acute high dose estrogen did not. The effects of a high soy diet were particularly evident in the parietal cortex and hippocampus, two regions protected by estrogen in animal models of neurological disease and injury. These results suggest that a high soy diet may provide beneficial effects to the brain similar to low dose chronic estrogen treatment such as that used for postmenopausal hormone replacement.

Effect of high soy diet on the cerebrovasculature and endothelial nitric oxide synthase in the ovariectomized rat

“…Recent data from our laboratory (Schreihofer et al 2005; Lovekamp-Swan et al 2007; Lovekamp-Swan et al 2007) and others (Setchell 2001; Lephart et al 2004; Burguete et al 2006) show a beneficial effect of a HS diet on the rodent brain. In particular, HS diets protect the brain from experimental ischemia and reduce apoptosis in the ischemic cortex (Schreihofer et al 2005; Burguete et al 2006; Lovekamp-Swan et al 2007).…”

Dietary genistein and equol (4′, 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia

“…An estimated 30 -50% of humans produce 4=, 7 isoflavandiol (equol) from gut microflora, but genistein and daidzein remain the primary circulating isoflavones even in equol producers (7, 30). In contrast, the daidzein metabolite equol (4=, 7 isoflavandiol) is the primary circulating isoflavone in rodents consuming soy diets and accounts for ϳ80% of plasma isoflavones (24,28,29). Genistein, daidzein, and equol all act as phytoestrogens with preferential affinity for estrogen receptor ␤ (ER␤) over ER␣ (21, 36), but equol is more potent than genistein or daidzein on ER␣ (21, 36).…”

Estrogen in combination with 5-azacitidine up-regulates p75NTR expression and induces apoptosis in 22Rv1 prostate cancer cells

“…A number of studies suggest that estrogen can alter the expression of neurotrophin receptors and perhaps even neurotrophins (16,17,35). We first demonstrated that estrogen enhances the expression of p75NTR in 22Rv1 prostate cancer cells, This effect occurs in association with the up-regulated expression of ESR2, suggesting that estrogen might not only directly regulate p75NTR expression, but may also influence the neurotrophin pathways via their receptors.…”