Roles of Astrocyte-Derived Estrogen in the Brain

Abstract

The steroid hormone, 17?-estradiol (E2) is an important hormone that regulates many functions in the body. Traditionally, E2 was believed to be produced primarily by the ovaries in females, but a number of studies have shown that brain cells such as neurons and astrocytes can also make significant quantities of E2. The study presented in this thesis examined the role of astrocyte-derived E2 in exerting neuroprotection in the CA1 region of the hippocampus, as well as its ability to regulate two specific pathways implicated in neuroprotection - the LIF and STAT3 pathways. Since the hippocampal CA1 region is known to be highly vulnerable to global cerebral ischemia (GCI), such as occurs after cardiac arrest, we used a mouse GCI model to examine the neuroprotective role of astrocyte-derived E2 in the hippocampal CA1 region. The results of the study indicate that mice that lack the enzyme aromatase in astrocytes and were unable to produce astrocyte-derived E2, have decreased reactive astrocyte activation after GCI, greater neuronal deficits after GCI in both genders, and they have significantly decreased LIF-STAT3 signaling in the hippocampus.