Ketogenic diet increases concentrations of kynurenic acid in discrete brain structures of young and adult rats

J Neural Transm (Vienna). 2012 Jun;119(6):679-84. doi: 10.1007/s00702-011-0750-2. Epub 2011 Dec 27.

Abstract

Targeting mechanisms that result in increased concentrations of kynurenic acid (KYNA) in the brain has been considered as a therapeutic approach for the treatment of epilepsy and certain neurodegenerative disorders. Recently, KYNA has been implicated in the effects produced by the high-fat and low-protein/carbohydrate ketogenic diet (KD) in a report demonstrating an increased production of KYNA in vitro by one of the ketone bodies, β-hydroxybutyrate, elevated by the KD. To further explore this association, brain concentrations of KYNA were compared in young (3 weeks old) and adult (8-10 weeks old) rats that were chronically exposed to the KD and regular diet. Exposure to the KD resulted in the anticipated elevations of β-hydroxybutyrate with accompanying decreases in glucose concentrations. In comparison to rats fed the regular diet, KYNA concentrations were significantly (p < 0.05) increased in the hippocampus (256 and 363% increase in young and adult rats, respectively) and in the striatum (381 and 191% increase in young and adult rats, respectively) in KD-fed rats. KD-induced increases in KYNA concentrations in young versus adult rats in the hippocampus and striatum were comparable (p > 0.05). Exposure to the KD had no effect on KYNA concentrations in the cortex of young and adult rats (p > 0.05). In summary, chronic exposure to the KD resulted in several-fold increases in KYNA concentrations in discrete brain structures in the rats. Thus, the relevant clinical question for further exploration is whether KD-induced increases in KYNA concentrations can translate into clinically significant improvements in neuropsychiatric diseases associated with KYNA hypofunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Aging / metabolism*
  • Animals
  • Blood Glucose / metabolism
  • Brain Chemistry / drug effects*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Diet, Ketogenic*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Kynurenic Acid / metabolism*
  • Rats
  • Rats, Inbred BN

Substances

  • Blood Glucose
  • Kynurenic Acid
  • 3-Hydroxybutyric Acid