Chemical Exposure-Induced Changes in the Expression of Neurotrophins and Their Receptors in the Main Olfactory System of Mice Lacking TRPM5-Expressing Microvillous Cells

Int J Mol Sci. 2018 Sep 27;19(10):2939. doi: 10.3390/ijms19102939.

Abstract

Functional maintenance of the mammalian main olfactory epithelium (MOE) is challenging because of its direct exposure to a wide spectrum of environmental chemicals. We previously reported that transient receptor potential channel M5-expressing microvillous cells (TRPM5-MCs) in the MOE play an important role in olfactory maintenance. To investigate the underpinning mechanisms, we exposed transcription factor Skn-1a knockout (Skn-1a-/-) mice lacking TRPM5-MCs, and TRPM5-GFP mice to either vehicle (water) or a mixture of odorous chemicals and chitin for two weeks and analyzed the expression of olfactory signaling proteins using immunolabeling and neurotrophin (NT) and NT receptor (NTR) gene transcripts using real-time quantitative PCR. The chemical exposure did not significantly attenuate the immunolabeling of olfactory signaling proteins. Vehicle-exposed Skn-1a-/- and TRPM5-GFP mice expressed similar levels of NT and NTR gene transcripts in the MOE and olfactory bulb. Chemical exposure significantly increased MOE expression of p75NTR in Skn-1a-/- mice, while p75NTR expression was reduced in TRPM5-GFP mice, as compared to vehicle-exposed mice. Additionally, our RNA in situ hybridization analysis and immunolabeling confirmed MOE expression of most NTs and NTRs. Together, these results indicate that TRPM5-MCs and chemical exposure influence expression of some NTs and NTRs in the MOE and olfactory bulb (OB).

Keywords: Skn-1a/Pou2f3; microvillous cells; olfactory epithelial maintenance; olfactory sensory neurons; real-time qPCR.

MeSH terms

  • Animals
  • Chitin / pharmacology
  • Ethylamines / pharmacology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Octamer Transcription Factors / genetics
  • Olfactory Receptor Neurons / drug effects
  • Olfactory Receptor Neurons / metabolism*
  • Receptors, Nerve Growth Factor / genetics*
  • Receptors, Nerve Growth Factor / metabolism
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism

Substances

  • Ethylamines
  • Nerve Growth Factors
  • Octamer Transcription Factors
  • Pou2f3 protein, mouse
  • Receptors, Nerve Growth Factor
  • Ngfr protein, mouse
  • TRPM Cation Channels
  • Trpm5 protein, mouse
  • Chitin
  • triethylamine