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Friday, March 28, 2014

Dravet syndrome (DS), also known as Severe Myoclonic Epilepsy of Infancy (SMEI), is a form of catastrophic epilepsy with a bleak prognosis. Seizures in DS start in early childhood, and children afflicted can exhibit symptoms aside from seizures such as behavioral, social and cognitive dysfunction.

DS is caused primarily by mutations in the SCN gene. This gene codes for the sodium (Na) channel, and aberrations in this channel can make the circuit hyperexcitable and susceptible to seizures.

Although we know the gene and ion channel involved in DS, it is not yet known how exactly this mutation affects neuronal circuits. A recent study in the journal Epilepsia attempted to answer this question.

The scientists used a mouse model of SMEI (mSMEI), and studied cellular and circuit properties of the brains of these mice. Since seizures in DS can be caused by fever, the researchers studied how high temperature (hyperthermia) would affect neuronal circuits.

Results with the mSMEI mouse model of DS:

  • Brain slices from mSMEI mice showed increased excitation and diminished inhibition in the hippocampus.

  • When seizures were induced by hyperthermia (reminiscent of a fever), brain slices from mSMEI mice showed a lower threshold to such seizures.

  • An agonist of adenosine – a known anticonvulsant – was able to control circuit hyperexcitability in brain slices from mSMEI mice.

This study showed that brains from mice with SMEI have dysfunctional neuronal circuits, and that adenosine can help control this hyperexcitability. Once we understand more about the mechanisms underlying DS, we can design targeted therapies for individuals with DS.

Authored by: Sloka Iyengar PhD on 3/2014
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