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

David N. Ruskin, Jessica L. Ross, Masahito Kawamura, Tiffany L. Ruiz, Jonathan D. Geiger, Susan A. Masino

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)501-507
Number of pages7
JournalPhysiology and Behavior
Volume103
Issue number5
DOIs
StatePublished - Jul 6 2011

Keywords

  • Body weight
  • Ketones
  • Lifespan
  • Motor coordination
  • Sex differences
  • Spontaneous alternation
  • Working memory

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

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