Aging
Navigate
Submit an Article
Research Paper|Volume 16, Issue 7|pp 5811—5828

The impact of continuous and intermittent ketogenic diets on cognitive behavior, motor function, and blood lipids in TgF344-AD rats

Jennifer M. Rutkowsky1, Zabrisky Roland1, Anthony Valenzuela1, An B. Nguyen1, Heui Hye Park1, Natalie Six1, Ilknur Dursun1,4, Kyoungmi Kim5, Pamela J. Lein1,2,3, Jon J. Ramsey1
  • 1Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
  • 2The MIND Institute, School of Medicine, University of California, Davis, CA 95817, USA
  • 3Center for Neuroscience, University of California, Davis, CA 95616, USA
  • 4Department of Physiology, School of Medicine, Istinye University, Istanbul 34396, Turkey
  • 5Department of Public Health Sciences, School of Medicine, University of California, Davis, CA 95616, USA
Received: September 15, 2023Accepted: March 13, 2024Published: April 12, 2024
https://doi.org/10.18632/aging.205741

Copyright: © 2024 Rutkowsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer’s disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating β-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.