Pharmacopsychiatry 2015; 25 - A28
DOI: 10.1055/s-0035-1557966

Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimerʼs disease mouse model

N Kunath 1, A Kumar 1, M Dozier-Sharpe 1, D B Allison 2, T Van Groen 1, I Kadish 1
  • 1Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, AL, USA
  • 2Office of Energetics, Nutrition Obesity Research Center, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA

We provide evidence for a differential role of a ghrelin agonist on glucose homeostasis in an Alzheimerʼs disease mouse model (Tg APPSwDI, C57BL/6 background) fed a high–glycemic index diet as a constant challenge for glucose homeostasis. The ghrelin agonist impaired glucose tolerance immediately after administration but not in the long term. At the same time, the ghrelin agonist improved spatial learning in the mice, raised their activity levels, and reduced their body weight and fat mass. Immunoassay results showed a beneficial impact of long-term treatment on insulin signaling pathways in hippocampal tissue. The present results suggest that ghrelin might improve cognition in Alzheimerʼs disease via a central nervous system mechanism involving insulin signaling.