Degree Name

Master of Science (MS)

Semester of Degree Completion

2002

Thesis Director

Britto P. Nathan

Abstract

Estrogen (E2) plasma levels fluctuate as a function of estrous cycling in the mouse. Apolipoprotein E (apoE) mRNA has been shown to increase in both hippocampal astrocytes and microglia during proestrus when plasma estrogen levels are high. The current study was designed to evaluate apoE localization and glial activation in mouse olfactory bulb (OB) as a function of the estrous cycle. In the rat OB, estrogen receptor β (ERβ) is present in the glomerular and external plexiform layers, but not the internal plexiform and granule cell layers. Normal female mice 2-3 months old at the start of the study were evaluated by vaginal smears for at least three weeks to assure normal estrous cycles. Three mice were sacrificed during diestrus, proestrus or estrus. The OB were collected and fixed for immunocytochemical techniques. Immunoreactive cell counts were made for apoE, glial fibrillary acidic protein (GFAP), an antigen elevated by activated astrocytes, and F4/80, an antigen elevated by activated microglia. Our studies found that estrus stage affected overall density of immunoreactive glial cells. ApoE levels covaried with E2 levels in the estrous cycle. During estrus, when E2 levels are declining, astrocyte immunoreactivity was highest in the glomerular, internal plexiform and granule cell layers suggesting a somewhat delayed response to E2. During proestrus and diestrus, when E2 levels are increasing, microglial density increased in the internal plexiform and granule cell layers suggesting a more immediate E2 effect. These data suggest that microglia and astrocytes respond to E2 in a time-dependent manner that is mediated through ERβ and other sequential cellular mechanisms.

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