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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging
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Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging

机译：鼻内胰岛素改善与年龄有关的认知缺陷并逆转脑衰老的电生理相关性

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Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca2+-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.
机译：周围胰岛素抵抗是与肥胖，血脂异常，高血压和2型糖尿病相关的代谢综合症的关键组成部分。胰岛素抵抗的影响在外周已得到公认，但在大脑中也已变得显而易见。最近的研究表明，胰岛素抵抗可能是大脑衰老和阿尔茨海默氏病（AD）的一个因素，鼻内胰岛素疗法将胰岛素输送到大脑，从而改善了AD患者的认知和记忆力。在这里，我们测试了一种临床相关的给药方法，以确定两种形式的胰岛素，即短效赖脯胰岛素（Humalog）或长效胰岛素德特米尔（Levemir）对老年F344大鼠认知功能的影响。我们还探讨了胰岛素对Ca2 +依赖性海马后超极化（AHP）的影响，AHP是衰老的一个很好表征的神经生理学标志，在衰老，记忆受损的动物中它会增加。低剂量鼻内胰岛素改善了老年动物的记忆记忆，因此其性能与年轻动物相似。此外，由于离体胰岛素还降低了AHP，因此我们的结果表明AHP可能是脑中胰岛素的新型细胞靶标，鼻内胰岛素治疗后认知功能的改善可能是胰岛素对AHP起作用的结果。

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