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Evolution And Epilepsy

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2009-01-21 12:46

Studies at the University of Pennsylvania School of Medicine on brain electrical signaling offer a fresh perspective on vertebrate evolution, provide additional evidence supporting Darwinian views of evolution, and may also lead to more effective treatment of epileptic seizures in infants. Researchers discovered how evolutionary changes produced a series of improvements in molecules generating electrical signals in nerves between 550 and 400 million years ago. By making nervous systems faster and smarter, these innovations appear to have contributed to the evolutionary success and diversity of vertebrate animals.

In an evolutionary comparison of nerve cell genes appearing in PLoS Genetics last month, Penn scientists show that improvements in the molecules that govern rapid nerve impulses occurred at major turning points in evolutionary history. By making nerve signals faster and more controllable, these innovations appear to have contributed to the building of smarter brains, and perhaps even to the success and diversity of vertebrates. In other experiments presented at the Society for Neuroscience meeting in November and soon to appear in the Annals of Neurology, the scientists found that the same electrical signaling molecules appear to be an effective target for anti-seizure drugs for human newborns.

The electrical signaling molecules at the center of both studies are two related types of nerve cell proteins called sodium and potassium channels. A decade ago, researchers found that mutations in genes for these molecules were a cause of some forms of epilepsy in newborn babies and infants. Sodium channels were already targets of anti-epileptic drugs. The team led by Assistant Professor of Neurology Edward C. Cooper, MD, PhD, focused on the potassium channels for therapeutic development.

Epilepsy is a common condition in which seizures, involuntary attacks of loss of awareness and bodily control, are experienced recurrently. Epilepsy can begin at any age, but incidence is highest in the vulnerable first few weeks of life and remains elevated in later infancy and early childhood.

Initial work by the Penn team showed that the potassium and sodium channels were clustered together in small patches on the long fibers, called axons, which transmit electrical impulses between nerve cells. This raised several questions from the both the evolutionary and clinical underpinnings of this line of research: First, how did these two types of channels evolve to become so tightly paired at these patches on nerves? Second, is the development of these clusters over time important for understanding how channel mutations cause epilepsy? Third, clinically, since the potassium channel mutations linked to newborn epilepsy decreased channel activity, could drugs that increased the potassium channel activity be effective for seizure prevention?

Anchoring Sequences

Sodium and potassium channels are proteins embedded in the nerve membrane, with a part of each channel exposed to the cell’s interior. In 2006, Cooper’s team showed that the intracellular parts of the potassium and sodium channels possessed similar amino acid sequences. The shared sequences contained instructions specifying that the channels should be anchored together at spots along the axon.

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