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

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.