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Updated: Sep 29, 2025
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Effect of a Ketogenic Diet on Oxidative Posttranslational Protein Modifications and Brain Homogenate Denaturation in
Pavlina Andreeva-Gateva1, Zafer Sabit2, Dimitar Bakalov2
1Department of Pharmacology and Toxicology, Faculty of Medicine, Medical University of Sofia, 1, Georgi Sofiiski Str., 1431, Sofia, Bulgaria. pandreeva_gateva@outlook.com.
Abstract:
This study focused on the ketogenic diet (KD) effects on oxidative posttranslational protein modification (PPM) as presumptive factors implicated in epileptogenesis. A 28-day of KD treatment was performed. The corneal kindling model of epileptogenesis was used. Four groups of adult male ICR mice (25-30 g) were randomized in standard rodent chow (SRC) group, KD-treatment group; SRC + kindling group; KD + kindling group (n = 10 each). Advanced oxidation protein products (AOPP) and protein carbonyl contents of brain homogenates together with differential scanning calorimetry (DSC) were evaluated. Two exothermic transitions (Exo1 and Exo2) were explored after deconvolution of the thermograms. Factor analysis was applied. The protective effect of KD in the kindling model was demonstrated with both decreased seizure score and increased seizure latency. KD significantly decreased glucose and increased ketone bodies (KB) in blood. Despite its antiseizure effect, the KD increased the AOPP level and the brain proteome's exothermic transitions, suggestive for qualitative modifications. The ratio of the two exothermic peaks (Exo2/Exo1) of the thermograms from the KD vs. SRC treated group differed more than twice (3.7 vs. 1.6). Kindling introduced the opposite effect, changing this ratio to 2.7 for the KD + kindling group. Kindling significantly increased glucose and KB in the blood whereas decreased the BW under the SRC treatment. Kindling decreased carbonyl proteins in the brain irrespectively of the diet. Further evaluations are needed to assess the nature of correspondence of calorimetric images of the brain homogenates with PPM.
Insights
The ketogenic diet (KD) shows protective effects against epilepsy in mice, reducing seizure severity. However, KD also alters protein modifications in the brain, suggesting complex interactions that require further investigation.
Area of Science:
- Neuroscience
- Biochemistry
- Metabolic Research
Background:
- Epileptogenesis involves complex molecular changes, including oxidative posttranslational protein modifications (PPM).
- The ketogenic diet (KD) is a recognized therapy for epilepsy, but its precise molecular mechanisms remain under investigation.
- Oxidative stress and protein modifications are implicated in neurological disorders, including epilepsy.
Purpose of the Study:
- To investigate the impact of the ketogenic diet (KD) on oxidative posttranslational protein modifications (PPM) in a mouse model of epileptogenesis.
- To evaluate the protective effects of KD against seizures and its influence on brain protein characteristics.
- To explore the relationship between KD, oxidative stress markers, and brain thermal properties.
Main Methods:
- Utilized a corneal kindling model of epileptogenesis in adult male ICR mice over 28 days.
- Administered standard rodent chow (SRC) or ketogenic diet (KD) to four experimental groups (SRC, KD, SRC+Kindling, KD+Kindling).
- Assessed advanced oxidation protein products (AOPP), protein carbonyl content, blood glucose, ketone bodies (KB), body weight (BW), and employed differential scanning calorimetry (DSC) with factor analysis.
Main Results:
- KD demonstrated a protective effect in the kindling model, decreasing seizure scores and increasing seizure latency.
- KD significantly reduced blood glucose and increased ketone bodies (KB), confirming dietary adherence.
- Despite antiseizure effects, KD increased AOPP levels and altered brain proteome's thermal transitions (Exo2/Exo1 ratio increased from 1.6 to 3.7), suggesting qualitative protein modifications.
Conclusions:
- The ketogenic diet exerts protective effects in an epilepsy model, likely through metabolic shifts and modulation of protein characteristics.
- KD induces oxidative protein modifications and alters brain thermal properties, indicating a complex interplay between diet, metabolism, and brain function.
- Further research is necessary to elucidate the specific PPM changes induced by KD and their direct correlation with its anticonvulsant mechanisms.
