Gene mutation causes symptoms of epileptic encephalopathy in mice, neuron death

In patients with epileptic encephalopathy (a form of severe congenital epilepsy), mice with genetic mutations have not only exhibited seizures, developmental and behavioral symptoms, but also neurodegeneration and brain inflammation.

Research leader and professor of molecular integrative physiology, Hei Zhengzhong, said: "Patients with epileptic encephalopathy begin to have seizures at birth, and exhibit progressive developmental delay, intellectual disability and autistic-like behavior

"The dogma of epileptic encephalopathy has always been that epileptic seizures promote the pathogenesis of intellectual disability and developmental delay

Previous work by Chung's team found that epileptic encephalopathy is related to a genetic mutation, and the potassium channels encoded by this gene are essential for regulating neuronal activity

In this new study, published in the Proceedings of the National Academy of Sciences, Chung’s team worked with Justin Rhodes, a professor of psychology, and Eli, a professor of molecular and integrated physiology.

These mice developed spontaneous seizures similar to those of human patients, and human patients began to have seizures in their infancy

He said: "What we are very interested in is that from a very young age, mice not only showed the same epileptic activity as human patients, but also showed the same mental, developmental and behavioral symptoms as human patients

In the brain, the researchers found that extensive neurodegeneration and inflammation began as early as weaning, and worsened as the mice got older

The researchers say these findings open up two potential therapeutic targets: potassium channel defects and inflammation and neurodegeneration

"Many patients with epileptic encephalopathy do not respond to antiepileptic drugs

Next, the researchers want to study the cause of neuronal death and whether other mutations in potassium channels can cause the same symptoms

Article title

Spontaneous seizure and memory loss in mice expressing an epileptic encephalopathy variant in the calmodulin-binding domain of Kv7.