Molecular Mechanisms of Intranasal Insulin in SAMP8 Mice.
Molecular Mechanisms of Intranasal Insulin in SAMP8 Mice.
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DOI：
10.3233/jad-190707
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Banks WA
中科院分区：
文献类型：
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作者：
Rhea EM;Nirkhe S;Nguyen S;Pemberton S;Bammler TK;Beyer R;Niehoff ML;Morley JE;Farr SA;Banks WA
在过去的十年中，药物、肽和蛋白质的鼻内递送的研究作为将底物递送到大脑的替代方式而发展。最近的研究表明，胰岛素的鼻内（INL）递送可改善健康受试者以及阿尔茨海默病（AD）患者和AD小鼠模型的记忆和认知。然而，胰岛素对记忆有益作用的分子机制仍不清楚。使用SAMP8 AD小鼠模型，我们研究了INL胰岛素对包括嗅球、下丘脑和海马在内的脑区蛋白质和基因表达的影响。我们发现胰岛素受体信号通路中的基因和蛋白质没有被测试剂量激活。然而，我们确实发现，海马体中参与其他途径的基因表达，特别是与炎症相关的基因表达，由于年龄和先前显示改善认知的INL胰岛素剂量而发生改变。当通过INL途径递送时，这些替代途径可能是胰岛素的靶点，以帮助改善记忆。
Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal (INL) delivery of insulin improves memory and cognition in healthy subjects as well as patients with Alzheimer’s disease (AD) and in AD mouse models. However, the molecular mechanism(s) for the beneficial effect of insulin on memory are still unclear. Using the SAMP8 mouse model of AD, we investigated the impact of INL insulin on protein and gene expression in brain regions including the olfactory bulb, hypothalamus, and hippocampus. We found genes and proteins in the insulin receptor signaling pathway were not activated by the doses tested. However, we did find the expression of genes present in the hippocampus involved in other pathways, especially those related to inflammation, were altered due to age and with a dose of INL insulin previously shown to improve cognition. These alternate pathways could be targets of insulin when delivered via the INL route to aid in memory improvement.