Drug Combinations Modulate Stem Cell Proliferation in the Subventricular Zone of 11‐month‐old Rats: Innate Gender Differences Could Explain Alzheimer's Susceptibility

Abstract

In this study, we tested the effect of 30 days of various drugs and drug combinations on the stem cell proliferation in the subventricular zone (SVZ) of the lateral brain ventricles of middle aged (10–12 month) normal Sprague Dawley rats, looking for any gender differences. The female rats should be post‐menopausal, and showed very low endogenous stem cell proliferation, significantly different from male rats (P<0.0001). Statins (1 mg/kg) and the combination of Fluoxetine (5 mg/kg), Simvastatin (1 mg/kg) and Ascorbic acid significantly increased stem cell proliferation in the anterior and middle SVZ in female rats, while the three drug combination increased stem cell proliferation in the posterior SVZ. In the male rats, Fluoxetine (5 mg/kg) significantly decreased stem cell proliferation in all regions of the SVZ (anterior, middle, and posterior). Simvastatin (1 mg/kg) significantly decreased stem cell proliferation in the anterior SVZ in male rats, but not in the middle or posterior SVZ. When comparing the stem cell proliferation in different regions across the two genders with a 2‐way ANOVA, we found that fluoxetine and simvastatin significantly decreased male stem cell proliferation compared to females, but the drug combinations of fluoxetine and statin or fluoxetine, statin and ascorbic acid removed these gender differences. The decreased innate stem cell proliferation in females post‐menopause may make them more susceptible to Alzheimer's disease, but we have shown the fluoxetine, simvastatin and ascorbic acid might be used to increase stem cell proliferation, potentially delaying onset of the disease.Support or Funding InformationWSU Women's in Science Giving Circle