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Theanine attenuates memory impairments induced by klotho gene depletion in mice
Food & Function ( IF 5.1 ) Pub Date : 2018-12-14 00:00:00 , DOI: 10.1039/c8fo01577e
Bao Trong Nguyen 1, 2, 3, 4, 5 , Naveen Sharma 1, 2, 3, 4, 5 , Eun-Joo Shin 1, 2, 3, 4, 5 , Ji Hoon Jeong 5, 6, 7, 8, 9 , Sung Hoon Lee 2, 5, 6, 8, 9 , Choon-Gon Jang 6, 10, 11, 12, 13 , Seung-Yeol Nah 5, 14, 15, 16, 17 , Toshitaka Nabeshima 18, 19, 20, 21, 22 , Yukio Yoneda 21, 23, 24, 25 , Hyoung-Chun Kim 1, 2, 3, 4, 5
Affiliation  

Theanine (γ-glutamylethylamide), an amino acid in tea, is a putative neuroprotective and antioxidant compound capable of improving lifespan and cognitive function. Because we previously reported cognitive dysfunction in klotho mutant mice via down-regulation of janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3), M1 muscarinic cholinergic receptor (M1 mAChR), and ERK signaling, we, therefore, investigated whether self-administration of theanine affects memory dysfunction in response to klotho gene depletion in mice, and whether theanine modulates the JAK2/STAT3, M1 mAChR, and ERK signaling network. Theanine significantly attenuated memory impairments in klotho mutant mice. Moreover, theanine self-administration significantly attenuated inhibitions of JAK2/STAT3 phosphorylation, M1 mAChR expression, and ERK1/2 phosphorylation in the hippocampus of klotho mutant mice. Consistently, AG490, a JAK2/STAT3 inhibitor, dicyclomine, an M1 mAChR antagonist, or U0126, an ERK1/2 inhibitor, significantly counteracted theanine-induced attenuation of memory impairment induced by klotho gene depletion in mice. Our study suggests that theanine attenuates memory impairments in a genetic aging model via up-regulation of JAK2/STAT3, M1 mAChR, and ERK signaling.

中文翻译:

茶氨酸可减轻小鼠klotho基因耗竭 所致的记忆障碍

茶中的氨基酸茶氨酸(γ-谷氨酰胺基酰胺)是一种公认​​的神经保护和抗氧化剂化合物,能够改善寿命和认知功能。因为我们之前曾报道过klotho突变小鼠通过下调janus激酶2(JAK2)和信号转导和转录激活因子(STAT3),M1毒蕈碱胆碱能受体(M1 mAChR)和ERK信号传导而引起的认知功能障碍,所以我们进行了研究茶氨酸的自我管理是否会影响小鼠的klotho基因耗尽,从而影响记忆功能,以及茶氨酸是否能调节JAK2 / STAT3,M1 mAChR和ERK信号网络。茶氨酸可显着降低klotho的记忆障碍突变小鼠。此外,茶氨酸的自我给药显着减弱了klotho突变小鼠海马中JAK2 / STAT3磷酸化,M1 mAChR表达和ERK 1/2磷酸化的抑制作用。一致地,AG490(一种JAK2 / STAT3抑制剂),二环胺(一种M1 mAChR拮抗剂)或U0126(一种ERK 1/2抑制剂)可显着抵消茶氨酸诱导的小鼠klotho基因耗竭诱导的记忆障碍的减轻。我们的研究表明茶氨酸通过上调JAK2 / STAT3,M1 mAChR和ERK信号传导来减轻遗传衰老模型中的记忆障碍。
更新日期:2018-12-14
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