Research Offers Insight Into Link Between Metabolism, Epilepsy

BAD-KATP channel axis involved in metabolic control of excitation and seizure response

FRIDAY, May 25 (HealthDay News) -- In mice, modifications to the BCL-2-associated agonist of cell death (BAD) protein -- a protein that reduces glucose metabolism -- induce an increase in metabolically responsive adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, and resistance to seizures, according to a study published in the May 24 issue of Neuron.

Noting that modifications in the BAD protein are known to alter brain metabolism, from glucose to ketone bodies, and that a high-fat (ketogenic) diet is known to reduce epileptic seizures, Alfredo Gimenez-Cassina, Ph.D., from the Dana-Farber Cancer Institute in Boston, and colleagues investigated the role of BAD in the seizure response.

The researchers found that the effects of BAD on glucose metabolism and ketone bodies involved phospho-regulation and did not involve its apoptotic function. Modifications in BAD that reduced glucose metabolism also activated KATP channels in neurons, which tended to suppress electrical activity. Mice with modified BAD showed resistance to behavioral and electrographic seizures, which was reversed when the KATP channels were knocked out.

"Our findings reveal BAD as a novel molecular player in the metabolic control of neuronal excitation that imparts robust changes in susceptibility to both behavioral and electrographic seizures," Gimenez-Cassina and colleagues conclude. "Small molecules modeled after BAD variants that promote ketone body catabolism over glucose metabolism may help uncover new therapeutic targets to treat epileptic disorders."

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