Central Nervous System Delivery of Intranasal Insulin : Mechanisms of Uptake and Effects on Cognition
Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Journal of Alzheimer's disease : JAD - 47(2015), 3 vom: 20., Seite 715-28 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Salameh, Therese S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.07.2016 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
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| doi: |
10.3233/JAD-150307 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM253053242 |
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| 100 | 1 | |a Salameh, Therese S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Central Nervous System Delivery of Intranasal Insulin |b Mechanisms of Uptake and Effects on Cognition |
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| 500 | |a Date Completed 06.07.2016 | ||
| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a cognition | |
| 650 | 4 | |a insulin | |
| 650 | 4 | |a intranasal administration | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Iodine Radioisotopes |2 NLM | |
| 650 | 7 | |a Nootropic Agents |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Protein Kinase C |2 NLM | |
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| 700 | 1 | |a Bullock, Kristin M |e verfasserin |4 aut | |
| 700 | 1 | |a Hujoel, Isabel A |e verfasserin |4 aut | |
| 700 | 1 | |a Niehoff, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Wolden-Hanson, Tami |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Junghyun |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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