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.
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Authors | Tomasz Żarnowski, Tomasz Chorągiewicz, Maria Tulidowicz-Bielak, Sebastian Thaler, Robert Rejdak, Iwona Żarnowski, Waldemar Andrzej Turski, Maciej Gasior |
Journal | Journal of neural transmission (Vienna, Austria : 1996)
(J Neural Transm (Vienna))
Vol. 119
Issue 6
Pg. 679-84
(Jun 2012)
ISSN: 1435-1463 [Electronic] Austria |
PMID | 22200857
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Kynurenic Acid
- 3-Hydroxybutyric Acid
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Topics |
- 3-Hydroxybutyric Acid
(blood)
- Aging
(metabolism)
- Animals
- Blood Glucose
(metabolism)
- Brain Chemistry
(drug effects)
- Cerebral Cortex
(drug effects, metabolism)
- Corpus Striatum
(drug effects, metabolism)
- Diet, Ketogenic
- Female
- Hippocampus
(drug effects, metabolism)
- Kynurenic Acid
(metabolism)
- Rats
- Rats, Inbred BN
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