Increased Hippocampal Afterdischarge Threshold in Ketogenic Diet is Accompanied by Enhanced Kynurenine Pathway Activity

The efficacy of a ketogenic diet (KD) in controlling seizure has been shown in many experimental and clinical studies, however, its mechanism of action still needs further clarification. The major goal of the present study was to investigate the influence of the commercially available KD and caloric...

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Bibliographic Details
Published in:Neurochemical research 2022-07, Vol.47 (7), p.2109-2122
Main Authors: Osuch, Bartosz, Kołosowska, Karolina, Chmielewska, Natalia, Turzyńska, Danuta, Sobolewska, Alicja, Szyndler, Janusz, Maciejak, Piotr
Format: Article
Language:English
Subjects:
Alternations
Amino acids
Anticonvulsants
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Chain branching
Diet
Dietary restrictions
Fatty acids
High fat diet
Hippocampus
Ketogenesis
Kynurenic acid
Low carbohydrate diet
Neurochemistry
Neurology
Neurosciences
Original Paper
Plasma
Seizures
Tryptophan
Valproic acid
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Summary:The efficacy of a ketogenic diet (KD) in controlling seizure has been shown in many experimental and clinical studies, however, its mechanism of action still needs further clarification. The major goal of the present study was to investigate the influence of the commercially available KD and caloric restriction (CR) on the hippocampal afterdischarge (AD) threshold in rats, and concomitant biochemical changes, specifically concerning the kynurenine pathway, in plasma and the hippocampus. As expected, the rats on the KD showed higher AD threshold accompanied by increased plasma β-hydroxybutyrate level compared to the control group and the CR rats. This group presented also lowered tryptophan and elevated kynurenic acid levels in plasma with similar changes in the hippocampus. Moreover, the KD rats showed decreased levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) in plasma and the hippocampus. No regular biochemical changes were observed in the CR group. Our results are analogous to those detected after single administrations of fatty acids and valproic acid in our previous studies, specifically to an increase in the kynurenine pathway activity and changes in peripheral and central BCAA and AAA levels. This suggests that the anticonvulsant effect of the KD may be at least partially associated with those observed biochemical alternations.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-022-03605-0