Long-term effects of estradiol replacement in the olfactory system.

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol treatment increased the number of mature neurons in the OE and glomerular synaptophysin in both genotypes, but the magnitude of increase was greater in the WT than in the KO mice. These data suggest that estrogen and apoE act synergistically to minimize the loss of mature sensory neurons and synapses following ovariectomy.

Acute responses to estradiol replacement in the olfactory system of apoE-deficient and wild-type mice.

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in the olfactory epithelium, and reactive astrocyte numbers in the olfactory bulb (OB) in both WT and KO mice. We also found that estradiol increased glomerular synaptophysin (Syn), but the magnitude of increase was potentiated by the presence of apoE. These data suggest that apoE may be necessary to elicit the complete effect of estradiol on Syn upregulation.