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Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer's models.
Nature Medicine ( IF 58.7 ) Pub Date : 2019-Jan-01 , DOI: 10.1038/s41591-018-0275-4 Mychael V Lourenco 1, 2, 3 , Rudimar L Frozza 1, 4 , Guilherme B de Freitas 1, 5 , Hong Zhang 3 , Grasielle C Kincheski 1, 2 , Felipe C Ribeiro 1, 2 , Rafaella A Gonçalves 5 , Julia R Clarke 1, 6 , Danielle Beckman 1 , Agnieszka Staniszewski 3 , Hanna Berman 3 , Lorena A Guerra 1, 2 , Letícia Forny-Germano 1 , Shelby Meier 7 , Donna M Wilcock 7 , Jorge M de Souza 8, 9 , Soniza Alves-Leon 8, 9 , Vania F Prado 10, 11, 12 , Marco A M Prado 10, 11, 12 , Jose F Abisambra 7 , Fernanda Tovar-Moll 13, 14 , Paulo Mattos 13, 15 , Ottavio Arancio 3, 16, 17 , Sergio T Ferreira 1, 2 , Fernanda G De Felice 1, 5, 18
Nature Medicine ( IF 58.7 ) Pub Date : 2019-Jan-01 , DOI: 10.1038/s41591-018-0275-4 Mychael V Lourenco 1, 2, 3 , Rudimar L Frozza 1, 4 , Guilherme B de Freitas 1, 5 , Hong Zhang 3 , Grasielle C Kincheski 1, 2 , Felipe C Ribeiro 1, 2 , Rafaella A Gonçalves 5 , Julia R Clarke 1, 6 , Danielle Beckman 1 , Agnieszka Staniszewski 3 , Hanna Berman 3 , Lorena A Guerra 1, 2 , Letícia Forny-Germano 1 , Shelby Meier 7 , Donna M Wilcock 7 , Jorge M de Souza 8, 9 , Soniza Alves-Leon 8, 9 , Vania F Prado 10, 11, 12 , Marco A M Prado 10, 11, 12 , Jose F Abisambra 7 , Fernanda Tovar-Moll 13, 14 , Paulo Mattos 13, 15 , Ottavio Arancio 3, 16, 17 , Sergio T Ferreira 1, 2 , Fernanda G De Felice 1, 5, 18
Affiliation
Defective brain hormonal signaling has been associated with Alzheimer's disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released on cleavage of the membrane-bound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impairs long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescues synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescues memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuates the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.
中文翻译:
与运动相关的 FNDC5/irisin 可挽救阿尔茨海默病模型中的突触可塑性和记忆缺陷。
有缺陷的大脑激素信号传导与阿尔茨海默病 (AD) 相关,AD 是一种以突触和记忆障碍为特征的疾病。Irisin 是一种运动诱导的肌动蛋白,在膜结合前体蛋白纤连蛋白 III 型结构域的蛋白 5 (FNDC5) 裂解时释放,该蛋白也在海马中表达。在这里,我们显示 FNDC5/irisin 水平在 AD 海马和脑脊液以及实验性 AD 模型中降低。敲低大脑 FNDC5/irisin 会损害小鼠的长期增强和新的物体识别记忆。相反,提高大脑中 FNDC5/irisin 的水平可以挽救 AD 小鼠模型中的突触可塑性和记忆力。FNDC5/irisin 的外周过度表达可挽救记忆障碍,而阻断外周或脑 FNDC5/irisin 会减弱体育锻炼对 AD 小鼠突触可塑性和记忆的神经保护作用。通过表明 FNDC5/irisin 是 AD 模型中运动有益效果的重要介质,我们的研究结果将 FNDC5/irisin 定位为能够对抗 AD 中的突触衰竭和记忆障碍的新型药物。
更新日期:2019-01-27
中文翻译:
与运动相关的 FNDC5/irisin 可挽救阿尔茨海默病模型中的突触可塑性和记忆缺陷。
有缺陷的大脑激素信号传导与阿尔茨海默病 (AD) 相关,AD 是一种以突触和记忆障碍为特征的疾病。Irisin 是一种运动诱导的肌动蛋白,在膜结合前体蛋白纤连蛋白 III 型结构域的蛋白 5 (FNDC5) 裂解时释放,该蛋白也在海马中表达。在这里,我们显示 FNDC5/irisin 水平在 AD 海马和脑脊液以及实验性 AD 模型中降低。敲低大脑 FNDC5/irisin 会损害小鼠的长期增强和新的物体识别记忆。相反,提高大脑中 FNDC5/irisin 的水平可以挽救 AD 小鼠模型中的突触可塑性和记忆力。FNDC5/irisin 的外周过度表达可挽救记忆障碍,而阻断外周或脑 FNDC5/irisin 会减弱体育锻炼对 AD 小鼠突触可塑性和记忆的神经保护作用。通过表明 FNDC5/irisin 是 AD 模型中运动有益效果的重要介质,我们的研究结果将 FNDC5/irisin 定位为能够对抗 AD 中的突触衰竭和记忆障碍的新型药物。