Insulin-like growth factor 2 rescues aging-related memory loss in rats.
Insulin-like growth factor 2 rescues aging-related memory loss in rats.
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DOI：
10.1016/j.neurobiolaging.2016.04.006
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发表时间：
2016-08
影响因子：
4.2
通讯作者：
Alberini CM
中科院分区：
文献类型：
--
作者：
Steinmetz AB;Johnson SA;Iannitelli DE;Pollonini G;Alberini CM
衰老伴随着记忆能力的下降，特别是影响依赖于大脑皮层系统的记忆，如情景记忆和外显记忆。随着老年人口的显著增加，预防或挽救记忆缺陷的需求迫在眉睫。然而，缺乏有效的治疗方法。在这里，我们表明，成熟形式的胰岛素样生长因子2（IGF-2），在海马中调节的肽的学习，所需的记忆巩固和促进记忆增强的年轻成年啮齿动物，在老年大鼠海马突触的水平显着降低。相比之下，未成熟形式proIGF-2的海马水平增加，表明IGF-2加工中的衰老相关缺陷。与此一致，老年大鼠与年轻成年大鼠相比缺乏前蛋白转化酶2的活性，这是一种可能介导IGF-2翻译后加工的酶。重组的成熟形式的IGF-2的海马给药挽救了老年大鼠的海马依赖性记忆缺陷以及工作记忆障碍。因此，IGF-2可能代表一种新的治疗途径，用于预防或逆转与衰老相关的认知障碍。
Aging is accompanied by declines in memory performance, and particularly affects memories that rely on hippocampal-cortical systems, such as episodic and explicit. With aged populations significantly increasing, the need for preventing or rescuing memory deficits is pressing. However, effective treatments are lacking. Here we show that the level of the mature form of insulin-like growth factor 2 (IGF-2), a peptide regulated in the hippocampus by learning, required for memory consolidation and a promoter of memory enhancement in young adult rodents, is significantly reduced in hippocampal synapses of aged rats. By contrast the hippocampal level of the immature form proIGF-2 is increased, suggesting an aging-related deficit in IGF-2 processing. In agreement, aged compared to young adult rats are deficient in the activity of proprotein convertase 2, an enzyme that likely mediates IGF-2 post-translational processing. Hippocampal administration of the recombinant, mature form of IGF-2 rescues hippocampal-dependent memory deficits as well as working memory impairment in aged rats. Thus, IGF-2 may represent a novel therapeutic avenue for preventing or reversing aging-related cognitive impairments.