Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u.12., Pécs, 7624, Hungary.
Szentágothai Research Center, Center for Neuroscience, University of Pécs, Ifjúság u. 20, Pécs, 7624, Hungary.
Geroscience. 2019 Oct;41(5):643-654. doi: 10.1007/s11357-019-00083-1. Epub 2019 Jul 20.
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.
瞬时受体电位锚蛋白 1（TRPA1）受体的表达不仅在背根神经节和三叉神经节中被证实，而且在不同的脑区（如海马体、下丘脑和皮质）中也被证实。然而，关于它们在中枢神经系统神经退行性和与年龄相关的疾病中的作用的数据仍然不清楚。我们的研究目的是探讨 TRPA1 在老年痴呆症小鼠模型中的潜在作用。为了研究衰老过程中的变化，我们使用了雄性年轻（3-4 个月大）和年老（18 个月大）的野生型（TRPA1；WT）和 TRPA1 受体基因缺失（TRPA1）小鼠。我们使用新物体识别（NOR）测试以及 Y 迷宫（YM）、放射臂迷宫（RAM）和 Morris 水迷宫（MWM）测试来评估记忆和学习技能的下降。在行为学研究中，我们在 NOR 和 RAM 中发现老年 TRPA1 小鼠的记忆明显丧失，但在 YM 和 MWM 测试中，年龄和基因对其没有影响。TRPA1 显示出明显的记忆缺失减少，这可以在 NOR 中看到更高的辨别指数和在 RAM 中更少的探索时间。此外，年轻的 TRPA1 动物在 RAM 中表现出明显较少的参考记忆错误，并且在 NOR、RAM 和 YM 中表现出明显更高的活动性，与年龄匹配的 WT 相比。我们目前的工作首次提供了证据，证明 TRPA1 受体介导了老年记忆衰退的恶化效应。了解其潜在机制可能为痴呆症的药物治疗开辟新的视角。
