The Impact of hormone therapy (birth control pills) on DEK protein expression in memory-related brain regions: Implications for Alzheimer's disease

Abstract

By Din Selmanovic, Neuroscience

Advisor: Matia Solomon

Presentation ID: Room415_1

Abstract: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder that primarily induces memory loss. Notably, women are more likely to be diagnosed with AD. The female-biased increase in AD diagnosis during aging may be due to loss of ovarian hormones (e.g., estrogens) and other unidentified factors. To this end, we have determined that an estrogen receptor-alpha responsive target gene (DEK) is significantly decreased in the brain of elderly women with dementia, but not in men. Further, we have determined that DEK loss induces AD-related pathology in cell lines and in female rodents, suggesting a sex-specific link between DEK and AD. One of the most common hormonal regimens for young women are birth control pills (BCP). Given that women are more likely to be diagnosed with AD, it is critical to understand if BCP use during the reproductive years impacts AD risk. Here, we investigated whether an experimental regimen designed to mimic a common form of monophasic birth control in young women impacted memory and DEK expression in AD-relevant brain regions (i.e., hippocampus, retrosplenial cortex) in female mice. Mice were adminstered pellets of estradiol (E2), progesterone (P4), progesterone and ethynyl estradiol (P4+EE), or cholesterol. A Y-maze test was used to assess spatial memory and immunohistochemistry was performed to analyze DEK expression in brain. Our findings suggest a complex effect of hormone treatment on brain and behavior in mice that may be due to the dose, age, or hormonal milieu (ovariectomized or intact).