Switching Off Gene Prevents Epilepsy in Mice

DURHAM, N.C. - Neurobiologists have found that switching off a single gene for a neuronal protein prevents epilepsy in a mouse model of human epilepsy. They said their research offers the hope of drugs that could prevent the alterations in the brain that cause the normal brain to become epileptic. Such drugs could prove far superior to current antiseizure drugs that only inhibit seizures in people who already have epilepsy, rather than preventing its development.

The researchers, led by professor and chair of neurobiology James McNamara, M.D., published their findings in the July 8, 2004, Neuron. Besides McNamara, other co-authors on the paper were Xiao-Ping He, M.D., and Robert Kotloski of Duke; and Serge Nef, Bryan Luikart and Luis Parada of the University of Texas Southwestern Medical Center. The research was sponsored by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

In the paper, the researchers reported studies exploring the effects of knocking out in mice two genes in the brain - called BDNF and TrkB. The protein that BDNF encodes is a neurotrophic factor - a neuronal protein that regulates the structure and function of synapses, the sites at which neurons communicate with one another. BDNF produces its effects by activating its receptor, TrkB. Earlier studies in the McNamara laboratory and others had shown marked increases in BDNF expression, and in the activation of the BDNF receptor, TrkB, during development of epilepsy. And earlier studies in other laboratories revealed that eliminating one of two copies of the BDNF gene markedly reduced the tendency to develop epilepsy. Thus the authors expected that eliminating both copies of either the BDNF or TrkB genes would prevent epilepsy.

The mice used in the experiments were those whose brains had been induced to become epileptic by a series of mild electrical stimuli