SOY PHYTOESTROGENS ENHANCE NEUROGENESIS IN THE RAT SUB VENTRICULAR ZONE

Purpose: The purpose of this study was to test the hypothesis that soy phytoestrogens enhance neuronal stem cell proliferation in the brain following ischemic injury similar to estrogen. Methods: Female Sprague-Dawley rats were randomly assigned to one of 3 groups soy-free diet + vehicle (Veh), soy-free diet + estrogen (E), or high soy diet (Soy). Rats were bilaterally ovariectomized and, after 4 weeks of treatment, underwent 90 minutes of middle cerebral artery occlusion (MCAO) or sham MCAO. Twenty-four hours after MCAO, rats were euthanized and brain sections were prepared for histology. Coronal brain sections encompassing the subventricular-proliferating zone (SVZ) were stained with Fluorojade B (FJB) to detect dying neurons. In alternate sections, immuno fluorescence staining for Ki67 was used to identify proliferation, and staining for doublecortin (DCX) was used to detect early neurogenesis. Microscopic images were digitally captured and analyzed manually. Results: Fluoro-Jade B staining revealed reduced injury in the E and Soy treated groups compared to Veh, in agreement with previous studies. In both the MCAO and sham groups, E and Soy increased proliferation (Ki67 staining) in the SVZ more than 2-fold compared to Veh. DCX double labeling revealed that the majority of these cells were of neuronal lineage. Conclusions: Because our results demonstrated higher amounts of Ki67 & DCX in the Soy and E groups compared to Veh, we conclude that a soy diet induces neuroproliferation in the SVZ both in the presence and absence of injury. Thus, in addition to its neuroprotective role, dietary soy may mimic the neurorestorative action of estrogen.