Important regulatory function of transient receptor potential ankyrin 1 receptors in age-related learning and memory alterations of mice

Éva Borbély,Maja Payrits,Erika Pintér,Ágnes Hunyady,Gréta Mező

doi:10.1007/s11357-019-00083-1

Éva Borbély, Maja Payrits + Show 3 more

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https://doi.org/10.1007/s11357-019-00083-1

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Journal: GeroScience	Publication Date: Jul 20, 2019
Citations: 20	License type: open-access

Affiliation: University of Pecs

Abstract

Expression of the transient receptor potential ankyrin 1 (TRPA1) receptor has been demonstrated not only in the dorsal root and trigeminal ganglia but also in different brain regions (e.g., hippocampus, hypothalamus, and cortex). However, data concerning their role in neurodegenerative and age-related diseases of the CNS is still indistinct. The aim of our study was to investigate the potential role of TRPA1 in a mouse model of senile dementia. For the investigation of changes during aging, we used male young (3–4-month-old) and old (18-month-old) wild-type (TRPA1+/+;WT) and TRPA1 receptor gene-deleted (TRPA1−/−) mice. Novel object recognition (NOR) test as well as Y maze (YM), radial arm maze (RAM), and Morris water maze (MWM) tests were used to assess the decline of memory and learning skills. In the behavioral studies, significant memory loss was detected in aged TRPA1+/+ mice with the NOR and RAM, but there was no difference measured by YM and MWM tests regarding the age and gene. TRPA1−/− showed significantly reduced memory loss, which could be seen as higher discrimination index in the NOR and less exploration time in the RAM. Furthermore, young TRPA1−/− animals showed significantly less reference memory error in the RAM and notably higher mobility in NOR, RAM, and YM compared with the age-matched WTs. Our present work has provided the first evidence that TRPA1 receptors mediate deteriorating effects in the old age memory decline. Understanding the underlying mechanisms could open new perspectives in the pharmacotherapy of dementia.

Highlights

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal, non-selective cation channel, which belongs to the TRP superfamily
Attenuated memory loss was detected in old TRPA1−/− animals by the Novel object recognition (NOR) compared with the TRPA1+/+ respective controls
In case of both old and young TRPA1−/− mice, the density maps show more colorful areas and the center zone is covered by blue color which cannot be detected in the case of the respective WTs (Fig. 1g–j)

Summary

Introduction

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal, non-selective cation channel, which belongs to the TRP superfamily It is widely expressed on neuronal and non-neuronal cell types (Nilius et al 2012). The highest level of expression can be detected in the nervous system—primarily in the dorsal root and trigeminal ganglia as well as in capsaicin-sensitive sensory nerve endings (Zygmunt and Högestätt 2014). It plays a crucial role in several physiological and pathophysiological processes: pain sensation (Kádková et al 2017; Hung and Tan 2018), inflammation (Koivisto et al 2014; Choi and Di Nardo 2018), and cancer (Büch et al 2018). They have found that TRPA1 is a key mediator of nociceptor sensitization only in aged animals in an adjuvantinduced arthritis model (Garrison and Stucky 2014)

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