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Ketogenic diet prevents seizures by enhancing brain energy production, increasing neuron stability

e longer treatment with the KD was necessary to increase the resistance to seizures, they concluded that changes in gene expression might hold the key to the diet's anticonvulsant effects.

To identify which genes might be involved, the researchers used microarray "gene chips" to examine changes in gene expression for more than 7,000 rat genes simultaneously. They focused on the hippocampus, a region of the brain known to play an important role in many kinds of epilepsies. More than 500 of the genes they examined were correlated with treatment with the KD. The most striking finding was the coordinated up-regulation of genes involved in energy metabolism.

To explain this genetic effect, the scientists first eliminated the possibility that the KD diet might cause enhanced production of GABA, a chemical messenger in the brain that helps limit seizure activity. They found that GABA levels in the hippocampus were unchanged with the KD.

To test whether energy reserves in hippocampal neurons were enhanced with the KD, they counted the number of energy "factories," or mitochondria, within cells using electron microscopy. They found that KD treatment significantly increased the number of mitochondria per unit area in the hippocampus. This finding, along with the concerted increase in the expression of genes encoding energy metabolic enzymes, led them to conclude that KD treatment enhances energy production in the hippocampus and may lead to improved neuronal stability.

Finally, the researchers tested whether brain tissue affected by the KD would be more resistant to low levels of glucose (an effect of seizures) because of their enhanced energy reserves. They found that synaptic communication in KD-fed rats was more resistant to low glucose levels than in control animals fed a regular diet.

The researchers believe their new knowledge could lead to the development of more effective drug treatments for epilepsy and brain damag
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
12-Nov-2005


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