Long-term effects of estradiol replacement in the olfactory system

Abstract

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s 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.

Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

“…Many controversial studies have reported altered olfactory sensitivity via central and peripheral effects that correlates with changes in steroid hormone level in females [ 8 , 9 , 43 – 48 ]. Nevertheless, studies focusing on the direct modulation of neurons in the OE are lacking, and the exact molecular mechanisms modulating olfactory perception are unknown.…”

Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake

“…It has also been shown that estradiol treatment in mice alters the olfactory epithelium [44]. After estradiol treatment, the astrocyte density and the thickness of the olfactory epithelium was increased.…”

Differences in peripheral sensory input to the olfactory bulb between male and female mice

“…A growing body of work shows that peripheral chemosensory signaling can be modified by experience and internal state 2 26 27 28 , as well as by the activity of structures that process multisensory information 29 . The main olfactory epithelium expresses α- and β-type estrogen receptors 30 , and estrogen replacement can protect against olfactory sensory neuron (OSN) loss in gonadectomized mice 31 32 , suggesting that sex and hormone effects could have a peripheral locus. Similarly, the vomeronasal organ undergoes state-dependent filtering in which sex hormones influence the responses of peripheral sensory neurons to specific chemical cues and consequently also behavioral responses to those cues 33 34 .…”