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

Tomasz Żarnowski, Tomasz Chorągiewicz, Maria Tulidowicz-Bielak, Sebastian Thaler, Robert Rejdak, Iwona Żarnowski, Waldemar Andrzej Turski, Maciej Gasior, Tomasz Żarnowski, Tomasz Chorągiewicz, Maria Tulidowicz-Bielak, Sebastian Thaler, Robert Rejdak, Iwona Żarnowski, Waldemar Andrzej Turski, Maciej Gasior

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.

Figures

Fig. 1
Fig. 1
Concentrations (mean ± SEM; n = 3–6/each structure) of KYNA (pmol/g wet tissue) in the hippocampus, cortex, and striatum in young and adult rats fed a regular diet (open bars) or the KD (solid bars). Asterisks represent significant difference in the KD versus standard diet-fed rats at p < 0.05 (*), p < 0.01 (**), or p < 0.001 (***); ns donates non-significant difference (Tukey test following significant ANOVA)

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