The Role of TRPA1 Channels in the Central Processing of Odours Contributing to the Behavioural Responses of Mice.

János Konkoly,Dóra Zelena,Erika Pintér,Alíz Szilágyi,Ammar Alomari,Angéla Kecskés,Zoltán Sándor,Viktória Kormos,Beatrix Szilágyi,Balázs Gaszner

doi:10.3390/ph14121336

Abstract

Transient receptor potential ankyrin 1 (TRPA1), a nonselective cation channel, contributes to several (patho)physiological processes. Smell loss is an early sign in several neurodegenerative disorders, such as multiple sclerosis, Parkinson’s and Alzheimer’s diseases; therefore, we focused on its role in olfaction and social behaviour with the aim to reveal its potential therapeutic use. The presence of Trpa1 mRNA was studied along the olfactory tract of mice by combined RNAscope in situ hybridisation and immunohistochemistry. The aversive effects of fox and cat odour were examined in parallel with stress hormone levels. In vitro calcium imaging was applied to test if these substances can directly activate TRPA1 receptors. The role of TRPA1 in social behaviour was investigated by comparing Trpa1 wild-type and knockout mice (KO). Trpa1 mRNA was detected in the olfactory bulb and piriform cortex, while its expression was weak in the olfactory epithelium. Fox, but not cat odour directly activated TRPA1 channels in TRPA1-overexpressing Chinese Hamster Ovary cell lines. Accordingly, KO animals showed less aversion against fox, but not cat odour. The social interest of KO mice was reduced during social habituation–dishabituation and social interaction, but not during resident–intruder tests. TRPA1 may contribute to odour processing at several points of the olfactory tract and may play an important role in shaping the social behaviour of mice. Thus, TRPA1 may influence the development of certain social disorders, serving as a potential drug target in the future.

Highlights

Smell loss is an early sign of neurodegeneration, our study focused on the role of Transient receptor potential ankyrin 1 (TRPA1) in olfaction
Trpa1 mRNA was poorly detectable in the Olfaction beginstract in the (OE) and did not colocalise with β-tubulin III (Figure 2a)
In the olfactory bulb (OB), the Trpa1 mRNA was colocalised in almost all cases with the neuronal marker, neuronal nuclear protein (NeuN), suggesting its almost exclusive neuronal presence (Figure 2b)

Summary

Introduction

Transient receptor potential ankyrin 1 (TRPA1), a nonselective cation channel, may contribute to several physiological and pathological processes, including neurodegeneration. In our previous studies we provided substantial evidence that the lack of this ion-channel in Trpa knockout (KO) animals decelerated the progression of diverse neurodegenerative processes (e.g., demyelination, fibre loss [1,2,3]), while the presence of TRPA1 ameliorated age-related memory decline [4]. Based on the role of TRPA1 receptors in the abovementioned pathological processes, we presume that this ion channel could be a promising therapeutic target in the treatment of these disorders. Smell loss is an early sign of neurodegeneration, our study focused on the role of TRPA1 in olfaction

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