Cellular and Molecular Mechanisms Underlying the Interaction of ApoE and Estrogen in Olfactory Neuronal Growth-Potential Relevance to Alzheimer\u27s Disease

In recent years, there have been many studies looking at estrogen therapy (ET) as a treatment for Alzheimer\u27s disease. Literature review suggests a close relationship between estrogen and apolipoprotein E (apoE) in the central nervous system. The mechanism underlying the interaction of apoE genotype with estrogen in the nervous system is not yet known. Therefore, the objectives of this research are 1) to determine the effects of estradiol treatment on basal cell proliferation and neuronal differentiation and 2) to identify the estrogen receptor subtype (ERα and ERβ) that mediates the increase of apoE levels, neurite outgrowth and neuronal numbers. Results show the numbers of bromodeoxyuridine (BrdU) positive cells are double in estradiol-treated culture as compared to control. This means that having more BrdU positive cells in estradiol-treated culture means that estrogen induces cellular proliferation. Furthermore, the results suggest there is a synergistic effect between estradiol and apoE to facilitate neurite outgrowth. Results from both selective estrogen receptor modulators and estrogen receptor KO experiments clearly suggest that the effects of estradiol on neurite outgrowth are mediated by ERα. Our data suggests that ERα is crucial in promoting neurite outgrowth. Lastly, estradiol increases neuronal numbers. This effect of estradiol is not dependent on ER subtypes as estrogen treatment increased neuronal numbers in both ERα and ERβ KO mice cultures. A fundamental principle in chronic neurological diseases is the clinical manifestations represent a failure of repair to keep pace with disease-caused degeneration. Dementia occurs when degenerative processes exceed regenerative responses. Thoroughly understanding the molecular pathway by which estrogen promotes neuronal growth is essential to design estrogen-like compounds that have maximal clinical benefits with minimal side effects