Important regulatory function of transient receptor potential ankyrin 1 receptors in age-related learning and memory alterations of mice
Important regulatory function of transient receptor potential ankyrin 1 receptors in age-related learning and memory alterations of mice
复制标题
DOI：
10.1007/s11357-019-00083-1
复制
发表时间：
2019-10-01
期刊：
影响因子：
5.6
通讯作者：
Pinter, Erika
中科院分区：
文献类型：
--
作者：
Borbely, Eva;Payrits, Maja;Pinter, Erika
瞬时受体电位锚蛋白 1 (TRPA1) 受体的表达不仅在背根和三叉神经节中存在，而且在不同的大脑区域（例如海马、下丘脑和皮质）中也有表达。然而，关于它们在中枢神经系统神经退行性和年龄相关疾病中的作用的数据仍然不明确。我们研究的目的是调查 TRPA1 在老年痴呆小鼠模型中的潜在作用。为了研究衰老过程中的变化，我们使用雄性年轻（3-4个月大）和年老（18个月大）野生型（TRPA1（+/+）；WT）和TRPA1受体基因缺失（TRPA1（-/-））小鼠。新物体识别（NOR）测试以及Y迷宫（YM）、径向臂迷宫（RAM）和莫里斯水迷宫（MWM）测试用于评估记忆和学习技能的下降。在行为研究中，在具有 NOR 和 RAM 的老年 TRPA1(+/+) 小鼠中检测到显着的记忆丧失，但 YM 和 MWM 测试在年龄和基因方面没有测量到差异。 TRPA1(-/-) 表现出显着减少的记忆丧失，这可以看作是 NOR 中较高的辨别指数和 RAM 中较少的探索时间。此外，与年龄匹配的野生动物相比，年轻的 TRPA1(-/-) 动物在 RAM 中表现出显着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移动性。我们目前的工作提供了第一个证据，证明 TRPA1 受体介导老年记忆衰退的恶化作用。了解潜在的机制可以为痴呆症的药物治疗开辟新的视角。
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.