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, 119 (6), 679-84

Ketogenic Diet Increases Concentrations of Kynurenic Acid in Discrete Brain Structures of Young and Adult Rats

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Ketogenic Diet Increases Concentrations of Kynurenic Acid in Discrete Brain Structures of Young and Adult Rats

Tomasz Żarnowski et al. J Neural Transm (Vienna).

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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References

    1. Appleton DB, Vivo DC. An experimental animal model for the effect of ketogenic diet on epilepsy. Proc Aust Assoc Neurol. 1973;10:75–80. - PubMed
    1. Baran H, Gramer M, Honack D, Loscher W. Systemic administration of kainate induces marked increases of endogenous kynurenic acid in various brain regions and plasma of rats. Eur J Pharmacol. 1995;286:167–175. doi: 10.1016/0014-2999(95)00443-O. - DOI - PubMed
    1. Bough KJ, Valiyil R, Han FT, Eagles DA. Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet. Epilepsy Res. 1999;35:21–28. doi: 10.1016/S0920-1211(98)00125-9. - DOI - PubMed
    1. Bough KJ, Gudi K, Han FT, Rathod AH, Eagles DA. An anticonvulsant profile of the ketogenic diet in the rat. Epilepsy Res. 2002;50:313–325. doi: 10.1016/S0920-1211(02)00086-4. - DOI - PubMed
    1. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol. 2006;60:223–235. doi: 10.1002/ana.20899. - DOI - PubMed

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