Long-term intranasal insulin aspart: A profile of gene expression, memory, and insulin receptors in aged F344 rats

Hilaree N. Frazier, Adam O. Ghoweri, Emily Sudkamp, Eleanor S. Johnson, Katie L. Anderson, Grant Fox, Keomany Vatthanaphone, Mengfan Xia, Ruei Lung Lin, Kendra E. Hargis-Staggs, Nada M. Porter, James R. Pauly, Eric M. Blalock, Olivier Thibault

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Intranasal insulin is a safe and effective method for ameliorating memory deficits associated with pathological brain aging. However, the impact of different formulations and the duration of treatment on insulin’s efficacy and the cellular processes targeted by the treatment remain unclear. Here, we tested whether intranasal insulin aspart, a short-acting insulin formulation, could alleviate memory decline associated with aging and whether long-term treatment affected regulation of insulin receptors and other potential targets. Outcome variables included measures of spatial learning and memory, autoradiography and immunohistochemistry of the insulin receptor, and hippocampal microarray analyses. Aged Fischer 344 rats receiving long-term (3 months) intranasal insulin did not show significant memory enhancement on the Morris water maze task. Autoradiography results showed that long-term treatment reduced insulin binding in the thalamus but not the hippocampus. Results from hippocampal immunofluorescence revealed age-related decreases in insulin immunoreactivity that were partially offset by intranasal administration. Microarray analyses highlighted numerous insulin-sensitive genes, suggesting insulin aspart was able to enter the brain and alter hippocampal RNA expression patterns including those associated with tumor suppression. Our work provides insights into potential mechanisms of intranasal insulin and insulin resistance, and highlights the importance of treatment duration and the brain regions targeted.

Original languageEnglish
Pages (from-to)1021-1030
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number6
StatePublished - 2020

Bibliographical note

Funding Information:
This work is supported by the National Institutes of Health (R01AG033649 to O.T., T32DK007778 to H.N.F., and T32AG057461 to A.O.G.).

Publisher Copyright:
© The Author(s) 2019.


  • Animal model
  • Antiaging
  • Cognitive decline

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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