Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging

Shaniya Maimaiti, Katie L. Anderson, Chris DeMoll, Lawrence D. Brewer, Benjamin A. Rauh, John C. Gant, Eric M. Blalock, Nada M. Porter, Olivier Thibault

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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 Ca2+-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.

Original languageEnglish
Pages (from-to)30-39
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume71
Issue number1
DOIs
StatePublished - Jul 15 2015

Bibliographical note

Publisher Copyright:
© 2015 The Author.

Keywords

  • Afterhyperpolarization
  • Calcium
  • Memory
  • Neuronal excitability
  • Type 2 diabetes

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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