Pain & Central Nervous System Week via NewsEdge :

2008 OCT 6 - (NewsRx.com) -- "The childhood epilepsy syndrome of benign familial neonatal convulsions (BFNC) exhibits the remarkable feature of clinical remission within a few weeks of onset and a favourable prognosis, sparing cognitive abilities despite persistent expression of the mutant KCNQ2 or KCNQ3 potassium channels throughout adulthood (see also Seizure). To better understand such dynamic neuroprotective plasticity within the developing brain, we introduced missense mutations that underlie human BFNC into the orthologous murine Kcnq2 (Kv7.2) and Kcnq3 (Kv7.3) genes," scientists in the United States report.

"Mutant mice were examined for altered thresholds to induced seizures, spontaneous seizure characteristics, hippocampal histology, and M-current properties of CA1 hippocampal pyramidal neurons. Adult Kcnq2(A306T/+) and Kcnq3(G311V/+) heterozygous knock-in mice exhibited reduced thresholds to electrically induced seizures compared to wild-type littermate mice. Both Kcnq2(A306T/A306T) and Kcnq3(G311V/G311V) homozygous mutant mice exhibited early onset spontaneous generalized tonic-clonic seizures concurrent with a significant reduction in amplitude and increased deactivation kinetics of the neuronal M-current. Mice had recurrent seizures into adulthood that triggered molecular plasticity including ectopic neuropeptide Y (NPY) expression in granule cells, but without hippocampal mossy fibre sprouting or neuronal loss. These novel knockin mice recapitulate proconvulsant features of the human disorder yet show that inherited M-current defects spare granule cells from reactive changes in adult hippocampal networks," wrote N.A. Singh and colleagues, University of Utah.

The researchers concluded: "The absence of seizure-induced pathology found in these epileptic mouse models parallels the benign neurodevelopmental cognitive profile exhibited by the majority of BFNC patients."

Singh and colleagues published their study in the Journal of Physiology - London (Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. Journal of Physiology - London, 2008;586(14):3405-3423).

For additional information, contact N.A. Singh, University of Utah, Dept. of Human Genetics, Salt Lake City, UT 84112, USA.

The publisher's contact information for the Journal of Physiology - London is: Blackwell Publishing, 9600 Garsington Rd., Oxford OX4 2DQ, Oxon, England.

<>

Return to Epilepsy News