Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice.
Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice.
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DOI：
10.15252/emmm.201404228
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发表时间：
2014-10
影响因子：
11.1
通讯作者：
Garcia-Osta A
中科院分区：
文献类型：
--
作者：
Pascual-Lucas M;Viana da Silva S;Di Scala M;Garcia-Barroso C;González-Aseguinolaza G;Mulle C;Alberini CM;Cuadrado-Tejedor M;Garcia-Osta A
最近发现胰岛素样生长因子2（IGF2）在大鼠和小鼠的记忆巩固中发挥关键作用，海马或全身给予重组IGF2可增强记忆。在这里，使用基于基因治疗的方法与腺相关病毒（AAV），我们表明，IGF2在老年野生型小鼠海马过度表达增强记忆，促进树突棘的形成。此外，我们报告说，IGF2的表达减少，在阿尔茨海默病患者的海马，这使我们假设，增加IGF2水平可能是有益的治疗疾病。因此，我们使用AAV系统将IGF 2或IGF 1递送到APP小鼠模型Tg2576的海马中，并证明IGF 2和胰岛素样生长因子1（IGF 1）挽救行为缺陷，促进树突棘形成并恢复正常的海马兴奋性突触传递。过度表达IGF2但不表达IGF1的Tg2576小鼠的大脑也显示淀粉样蛋白水平显著降低。这种减少可能通过与IGF2受体（IGF2R）的相互作用发生。因此，IGF2和IGF1在较小程度上可能是阿尔茨海默病的有效治疗方法。
Insulin-like growth factor 2 (IGF2) was recently found to play a critical role in memory consolidation in rats and mice, and hippocampal or systemic administration of recombinant IGF2 enhances memory. Here, using a gene therapy-based approach with adeno-associated virus (AAV), we show that IGF2 overexpression in the hippocampus of aged wild-type mice enhances memory and promotes dendritic spine formation. Furthermore, we report that IGF2 expression decreases in the hippocampus of patients with Alzheimer's disease, and this leads us to hypothesize that increased IGF2 levels may be beneficial for treating the disease. Thus, we used the AAV system to deliver IGF2 or IGF1 into the hippocampus of the APP mouse model Tg2576 and demonstrate that IGF2 and insulin-like growth factor 1 (IGF1) rescue behavioural deficits, promote dendritic spine formation and restore normal hippocampal excitatory synaptic transmission. The brains of Tg2576 mice that overexpress IGF2 but not IGF1 also show a significant reduction in amyloid levels. This reduction probably occurs through an interaction with the IGF2 receptor (IGF2R). Hence, IGF2 and, to a lesser extent, IGF1 may be effective treatments for Alzheimer's disease.
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DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
DOI：
10.1073/pnas.0600948103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Jacobsen, JS;Wu, CC;Bloom, FE
通讯作者：
Bloom, FE
影响因子：
3
作者：
GLASER, EM;VANDERLOOS, H
通讯作者：
VANDERLOOS, H
影响因子：
2.4
作者：
Cline BH;Steinbusch HW;Malin D;Revishchin AV;Pavlova GV;Cespuglio R;Strekalova T
通讯作者：
Strekalova T