A Ketogenic Diet Delays Weight Loss and Does Not Impair Working Memory or Motor Function in the R6/2 1J Mouse Model of Huntington's Disease

Physiol Behav. 2011 Jul 6;103(5):501-7. doi: 10.1016/j.physbeh.2011.04.001. Epub 2011 Apr 9.

Abstract

Ketogenic diets are high in fat and low in carbohydrates, and have long been used as an anticonvulsant therapy for drug-intractable and pediatric epilepsy. Additionally, ketogenic diets have been shown to provide neuroprotective effects against acute and chronic brain injury, including beneficial effects in various rodent models of neurodegeneration. Huntington's disease is a progressive neurodegenerative disease characterized by neurological, behavioral and metabolic dysfunction, and ketogenic diets have been shown to increase energy molecules and mitochondrial function. We tested the effects of a ketogenic diet in a transgenic mouse model of Huntington's disease (R6/2 1J), with a focus on life-long behavioral and physiological effects. Matched male and female wild-type and transgenic mice were maintained on a control diet or were switched to a ketogenic diet fed ad libitum starting at six weeks of age. We found no negative effects of the ketogenic diet on any behavioral parameter tested (locomotor activity and coordination, working memory) and no significant change in lifespan. Progressive weight loss is a hallmark feature of Huntington's disease, yet we found that the ketogenic diet-which generally causes weight loss in normal animals-delayed the reduction in body weight of the transgenic mice. These results suggest that metabolic therapies could offer important benefits for Huntington's disease without negative behavioral or physiological consequences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Age Factors
  • Animals
  • Diet, Ketogenic / methods
  • Diet, Ketogenic / psychology*
  • Disease Models, Animal
  • Female
  • Humans
  • Huntingtin Protein
  • Huntington Disease / blood
  • Huntington Disease / diet therapy*
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology
  • Huntington Disease / psychology
  • Kaplan-Meier Estimate
  • Longevity / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory, Short-Term / drug effects*
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Rotarod Performance Test / methods
  • Sex Characteristics
  • Weight Loss / drug effects*
  • Weight Loss / physiology

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nuclear Proteins
  • 3-Hydroxybutyric Acid