Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat brain hippocampi of animals fed the ketogenic diet (KD) to provide insight into the anticonvulsant action of KD

ABSTRACT: The ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies. The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action. Using the Affymetrix rat arrays (RAE230A), 6 control samples and 5 KD samples were run.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Eric Hoffman

PROVIDER: E-GEOD-1155 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet.

Bough Kristopher J KJ Wetherington Jonathon J Hassel Bjørnar B Hassel Bjørnar B Pare Jean Francois JF Gawryluk Jeremy W JW Greene James G JG Shaw Renee R Smith Yoland Y Geiger Jonathan D JD Dingledine Raymond J RJ

Annals of neurology 20060801 2

<h4>Objective</h4>The full anticonvulsant effect of the ketogenic diet (KD) can require weeks to develop in rats, suggesting that altered gene expression is involved. The KD typically is used in pediatric epilepsies, but is effective also in adolescents and adults. Our goal was to use microarray and complementary technologies in adolescent rats to understand its anticonvulsant effect.<h4>Methods</h4>Microarrays were used to define patterns of gene expression in the hippocampus of rats fed a KD o ...[more]

PMID: 16807920

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Project description:Epilepsy affects between 1-2% of people worldwide and is defined symptomatically by the appearance of spontaneous, recurrent seizures. The ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies. Both clinical and experimental reports show that the KD can be used to treat a variety of seizure types. During KD treatment, ketone bodies, rather than glucose, become the major energy substrate for the brain; somehow, metabolic conversion confers a potent anticonvulsant effect. The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action. Despite its use for over 80 years, the mechanism of the diet remains unknown. It is expected that this work will help elucidate the underlying anticonvulsant action of the KD and contribute to future, rationale-based drug development. We propose to identify sets of genes activated/repressed within hippocampus after treatment with a KD. We hypothesize that gene expression patterns induced by alterations in metabolic pathways are critically involved with the anticonvulsant effects of the KD in mice. Mice (n=44, 129svJ) will be used for these experiments. Animals will be fed either a KD (n=22) or control diet (n=22) for 14 days. After this time, ten animals from each group will be subjected to flurothyl seizure testing to confirm seizure threshold elevation. Of the remaining KD- (n=12) or control-fed (n=12) animals, two left hippocampi will be pooled together such that six arrays from each treatment group can be tested. This is expected to reduce biological variability. Right hippocampi (n=12/group) will be maintained in our lab for corroborative analysis via RT-PCR and immunohistochemistry. All tissue samples will be rapidly dissected, frozen in liquid nitrogen, and stored at -80C until shipping/corroborative testing. Data analysis will be completed with Significance of Array Measurement (SAM) program using ANOVA from protection for multiple comparisons. Please use the Affy chip with known genes in lieu of the chip containing mostly EST's.

Dataset Information

Transcription profiling of rat brain hippocampi of animals fed the ketogenic diet (KD) to provide insight into the anticonvulsant action of KD

Publications

Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet.

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