Proteasome Activation by Insulin-like Growth Factor-1/Nuclear Factor Erythroid 2-related Factor 2 Signaling Promotes Exercise-induced Neurogenesis,STEM CELLS

当前位置： X-MOL 学术 › STEM CELLS › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Proteasome Activation by Insulin-like Growth Factor-1/Nuclear Factor Erythroid 2-related Factor 2 Signaling Promotes Exercise-induced Neurogenesis
STEM CELLS ( IF 4.0 ) Pub Date : 2019-11-13 , DOI: 10.1002/stem.3102
Xiaojie Niu ₁ , Yunhe Zhao ₁ , Na Yang ₁ , Xuechun Zhao ₁ , Wei Zhang _{1,

2} , Xiaowen Bai ₃ , Ang Li ₂ , Wulin Yang _{4,

5} , Li Lu ₁

Affiliation

Physical exercise‐induced enhancement of learning and memory and alleviation of age‐related cognitive decline in humans have been widely acknowledged. However, the mechanistic relationship between exercise and cognitive improvement remains largely unknown. In this study, we found that exercise‐elicited cognitive benefits were accompanied by adaptive hippocampal proteasome activation. Voluntary wheel running increased hippocampal proteasome activity in adult and middle‐aged mice, contributing to an acceleration of neurogenesis that could be reversed by intrahippocampal injection of the proteasome inhibitor MG132. We further found that increased levels of insulin‐like growth factor‐1 (IGF‐1) in both serum and hippocampus may be essential for exercise‐induced proteasome activation. Our in vitro study demonstrated that IGF‐1 stimulated proteasome activity in cultured adult neural progenitor cells (NPCs) by promoting nuclear translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2), followed by elevated expressions of proteasome subunits such as PSMB5. In contrast, pretreating adult mice with the selective IGF‐1R inhibitor picropodophyllin diminished exercise‐induced neurogenesis, concurrent with reduced Nrf2 nuclear translocation and proteasome activity. Likewise, lowering Nrf2 expression by RNA interference with bilateral intrahippocampal injections of recombinant adeno‐associated viral particles significantly suppressed exercise‐induced proteasome activation and attenuated cognitive function. Collectively, our work demonstrates that proteasome activation in hippocampus through IGF‐1/Nrf2 signaling is a key adaptive mechanism underlying exercise‐related neurogenesis, which may serve as a potential targetable pathway in neurodegeneration.

中文翻译：

胰岛素样生长因子 1/核因子红系 2 相关因子 2 信号传导对蛋白酶体的激活促进运动诱导的神经发生

体育锻炼诱导的学习和记忆增强以及缓解人类与年龄相关的认知能力下降已得到广泛认可。然而，运动与认知改善之间的机制关系在很大程度上仍然未知。在这项研究中，我们发现运动引起的认知益处伴随着适应性海马蛋白酶体的激活。自愿轮跑增加了成年和中年小鼠的海马蛋白酶体活性，有助于加速神经发生，这可以通过在海马内注射蛋白酶体抑制剂 MG132 来逆转。我们进一步发现血清和海马中胰岛素样生长因子-1 (IGF-1) 水平的增加可能对运动诱导的蛋白酶体激活至关重要。我们的体外研究表明，IGF-1 通过促进核因子红细胞 2 相关因子 2 (Nrf2) 的核易位，随后提高蛋白酶体亚基如 PSMB5 的表达，从而刺激培养的成人神经祖细胞 (NPC) 中的蛋白酶体活性。相比之下，用选择性 IGF-1R 抑制剂鬼臼苦素预处理成年小鼠会减少运动诱导的神经发生，同时减少 Nrf2 核易位和蛋白酶体活性。同样，通过 RNA 干扰双侧海马内注射重组腺相关病毒颗粒来降低 Nrf2 表达显着抑制了运动诱导的蛋白酶体激活并减弱了认知功能。总的来说，

更新日期：2019-11-13

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11