Long-term effects of estradiol replacement in the olfactory system

Exp Neurol. 2012 Sep;237(1):1-7. doi: 10.1016/j.expneurol.2012.06.001. Epub 2012 Jun 9.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / biosynthesis
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Biomarkers / metabolism
  • Estradiol / administration & dosage
  • Estradiol / physiology*
  • Estrogen Replacement Therapy
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Olfactory Pathways / metabolism*
  • Olfactory Pathways / pathology
  • Olfactory Pathways / physiopathology*
  • Ovariectomy
  • Random Allocation
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / metabolism
  • Synapses / pathology
  • Time Factors

Substances

  • Apolipoproteins E
  • Biomarkers
  • Estradiol