Molecular Mechanisms of Intranasal Insulin in SAMP8 Mice
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Journal of Alzheimer's disease : JAD - 71(2019), 4 vom: 01., Seite 1361-1373 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rhea, Elizabeth M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.11.2020 Date Revised 26.08.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.3233/JAD-190707 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM301690502 |
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| 245 | 1 | 0 | |a Molecular Mechanisms of Intranasal Insulin in SAMP8 Mice |
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| 500 | |a Date Completed 06.11.2020 | ||
| 500 | |a Date Revised 26.08.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a RNA sequence analysis | |
| 650 | 4 | |a cognition | |
| 650 | 4 | |a hippocampus | |
| 650 | 4 | |a insulin | |
| 650 | 4 | |a intranasal | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Nootropic Agents |2 NLM | |
| 650 | 7 | |a Receptor, Insulin |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Nirkhe, Surabhi |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Pemberton, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Bammler, Theo K |e verfasserin |4 aut | |
| 700 | 1 | |a Beyer, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Niehoff, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Morley, John E |e verfasserin |4 aut | |
| 700 | 1 | |a Farr, Susan A |e verfasserin |4 aut | |
| 700 | 1 | |a Banks, William A |e verfasserin |4 aut | |
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