Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers.
Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers.
复制标题
DOI：
10.1016/j.neuron.2012.12.040
复制
发表时间：
2013-03-06
期刊：
影响因子：
16.2
通讯作者：
Selkoe DJ
中科院分区：
文献类型：
--
作者：
Li S;Jin M;Zhang D;Yang T;Koeglsperger T;Fu H;Selkoe DJ
关于人类大脑衰老的一个中心问题是，认知丰富是否会减缓阿尔茨海默病的发展。在这里，我们表明，长时间暴露于丰富的环境（EE）促进信号在野生型小鼠的海马，促进长时程增强。EE效应的一个关键特征是β2-肾上腺素能受体和下游cAMP/PKA信号传导的激活。这种EE途径阻止了从AD皮质分离的可溶性淀粉样β蛋白（Aβ）寡聚体对LTP的抑制。EE的保护作用发生在年轻和中年野生型小鼠中。接触新奇事物比有氧运动提供更大的保护。长期喂食β-肾上腺素能激动剂而不含EE的小鼠可通过Aβ寡聚体保护海马损伤。因此，EE通过激活β-肾上腺素受体信号传导和减轻人Aβ寡聚体的突触毒性来增强海马突触可塑性。这些机制性见解支持使用长期暴露于认知新奇和/或口服β-肾上腺素能激动剂来减轻衰老期间Aβ蓄积的影响。
A central question about human brain aging is whether cognitive enrichment slows the development of Alzheimer changes. Here we show that prolonged exposure to an enriched environment (EE) facilitated signaling in the hippocampus of wild-type mice that promoted long-term potentiation. A key feature of the EE effect was activation of β2-adrenergic receptors and downstream cAMP/PKA signaling. This EE pathway prevented LTP inhibition by soluble oligomers of amyloid β-protein (Aβ) isolated from AD cortex. Protection by EE occurred in both young and middle-aged wild-type mice. Exposure to novelty afforded greater protection than did aerobic exercise. Mice chronically fed a β-adrenergic agonist without EE were protected from hippocampal impairment by Aβ oligomers. Thus, EE enhances hippocampal synaptic plasticity by activating β-adrenoceptor signaling and mitigating synaptotoxicity of human Aβ oligomers. These mechanistic insights support using prolonged exposure to cognitive novelty and/or oral β-adrenergic agonists to lessen the effects of Aβ accumulation during aging.
登录
查看更多内容
影响因子：
2
作者：
King, Stanley O., II;Williams, Cedric L.
通讯作者：
Williams, Cedric L.
DOI：
10.1523/jneurosci.0203-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li S;Jin M;Koeglsperger T;Shepardson NE;Shankar GM;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
4.2
作者：
Grudzien, Aneta;Shaw, Pamela;Mesulam, M. Marsel
通讯作者：
Mesulam, M. Marsel
影响因子：
2
作者：
Gelinas, Jennifer N.;Tenorio, Gustavo;Nguyen, Peter V.
通讯作者：
Nguyen, Peter V.
DOI：
10.1093/cercor/bhp065
发表时间：
2009-12
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Lemon N;Aydin-Abidin S;Funke K;Manahan-Vaughan D
通讯作者：
Manahan-Vaughan D