title: Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.
abstract: 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 Ca(2+)-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.
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Shaniya
authors: S
authors: Maimaiti
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Katie L
authors: KL
authors: Anderson
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Chris
authors: C
authors: DeMoll
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Lawrence D
authors: LD
authors: Brewer
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Benjamin A
authors: BA
authors: Rauh
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: John C
authors: JC
authors: Gant
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Eric M
authors: EM
authors: Blalock
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky.
authors: Nada M
authors: NM
authors: Porter
authors: Department of Pharmacology and Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky. othibau@uky.edu.
authors: Olivier
authors: O
authors: Thibault
mesh_terms: D000281:Administration, Intranasal; D000375:Aging / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism; D000069057:Insulin Detemir / Q000008:administration & dosage / Q000378:metabolism; D061268:Insulin Lispro / Q000008:administration & dosage / Q000378:metabolism; D007333:Insulin Resistance; D008568:Memory / Q000187:drug effects; D051381:Rats; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D061268:Insulin Lispro; D000069057:Insulin Detemir
keywords: Afterhyperpolarization.; Calcium; Memory; Neuronal excitability; Type 2 diabetes