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

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.

Role of Oxidative Stress and Ca2+ Signaling in Psychiatric Disorders

“…Interestingly, TRPA1 in astrocytes is implicated to partially contribute to cuprizone-induced demyelination, which is frequently used for the animal model of multiple sclerosis ( Kriszta et al, 2020 ), raising the possibility that there is a connection between TRPA1 expression or function and psychiatric disorders. Notably, another behavioral analysis using aged (18-month-old) Trpa1 KO mice supports the notion that TRPA1 negatively regulates hippocampal functions in an age-dependent manner ( Borbély et al, 2019 ) ( Table 2 ). Thus, these lines of evidence suggest that TRPA1 is a negative regulator of brain functions, raising the possibility that there is a connection between TRPA1 expression or function and psychiatric disorders; however, further studies are required to validate this hypothesis.…”

Ginsenoside Re protects against chronic restraint stress‐induced cognitive deficits through regulation of NLRP3 and Nrf2 pathways in mice

“…The Y-maze was used to evaluate the discrimination and spatial working memory of animals (Borbély, Payrits, Hunyady, Mez} o, & Pintér, 2019), using the ANY-maze animal behavior analysis system (Stoelting, USA).…”

Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction

“…[84] Moreover, the implication of TRPA1 receptors in the detrimental changes to memory that occur in the elderly has been recently reported. [85] Although the physiological role of TRPV4 is unclear, its role in brain pathologies and injuries characterized by inflammation and impairment has been well defined. [59,60] Recently, the relevance of TRPV4 in cerebrovascular function was highlighted when researchers found an impairment in the cognitive function of mice lacking the channel protein.…”

“…In particular, dramatic changes in the membrane expression and/or gain/ loss of function of inwardly rectifying potassium channel Kir4.1, excitatory amino acid transporter 2 (EAAT2), the gap junction protein connexin 43 (Cx43), the calcium channel TRPV4 and of the water channel AQP4 have been abundantly reported in pathological animal models and in humans. [6][7][8][9][83][84][85]128] Since astrocytes are an integral part of brain circuits, constantly interacting with neurons and blood vessels, it is important to develop materials and technologies that are able to interface with astrocytes and that are compatible with technologies already available for interfacing with neurons. Designing glial interfacing devices with these considerations in mind will allow scientist to generate a platform to gain new insight into brain function.…”