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

Abdullah Almatrouk,Wangmei Luo,Weihong Lin,Tatsuya Ogura,Chantel Wilson,Kayla Lemons

doi:10.3390/ijms19102939

Abdullah Almatrouk, Wangmei Luo + Show 4 more

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https://doi.org/10.3390/ijms19102939

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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).

Highlights

The sense of smell, initiated by the main olfactory epithelium (MOE) in the nasal cavity, provides animals and humans with information vital for their survival, as it enables them to assess food quality, detect pathogens, avoid predators, and find mating partners
Our results provide evidence that the expression of some NT and NT receptor (NTR) gene transcripts is influenced by chemical exposure and TRPM5-microvillous cells (MCs) in the MOE, providing a potential mechanism underlying the protective function of TRPM5-MCs
brain-derived neurotrophic factor (BDNF): p < 0.001; NT-3 vs. nerve growth factor (NGF): p < 0.001; NT-3 vs. NT-4: p < 0.001, n = 6 mice).5 of 21 These results revealed the relative abundances of NTs and NTRs in the mouse MOE

Summary

Introduction

The sense of smell, initiated by the main olfactory epithelium (MOE) in the nasal cavity, provides animals and humans with information vital for their survival, as it enables them to assess food quality, detect pathogens, avoid predators, and find mating partners. Due to its direct contact with the external environment, the MOE is exposed to a wide variety of inhaled chemicals including odorants, and irritants, toxicants, and pathogenic microorganisms. Some of these substances can cause structural and functional damage depending on the type of molecules, exposure levels, and durations [1,2,3]. Chronic exposure to these harmful substances contributes to the development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases [4]. Protective mechanisms against environmental insults are poorly understood, especially under chronic mild exposure, which is known to disturb brain function and behavior [5]

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