title: Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition.
abstract: 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.
authors.affiliation: Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.|Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Therese S
authors.initials: TS
authors.lastname: Salameh
authors.affiliation: Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Bullock
authors.affiliation: Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Isabel A
authors.initials: IA
authors.lastname: Hujoel
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA.|Veterans Affairs Medical Center-St. Louis, St. Louis, MO, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Niehoff
authors.affiliation: Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Tami
authors.initials: T
authors.lastname: Wolden-Hanson
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Morley
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA.|Veterans Affairs Medical Center-St. Louis, St. Louis, MO, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Farr
authors.affiliation: Geriatrics Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.|Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D018697:Nootropic Agents; D011994:Recombinant Proteins; D011493:Protein Kinase C
keywords: Alzheimer’s disease; cognition; insulin; intranasal administration