Neural Distress

Why different malfunctions may lead to similar patient problems.

The nervous system is an enormously complex, marvelously efficient system. At its core are hundreds of millions of neurons, specialized cells that work together to form highly coordinated pathways for transmitting electrical and chemical signals to and from the brain and spinal cord.

When neurons malfunction, systems break down. The resulting damage can cause a range of serious maladies, among them epilepsy, irregular heartbeats and mental illnesses. Treating these conditions is difficult, in part because doctors have trouble determining whether a drug that helps one patient will be effective in assisting another.

In a study published earlier this year, Joseph Ransdell, an MU doctoral student, Satish Nair, a professor of electrical and computer engineering, and David Schulz, an associate professor of biological sciences whose work was featured in the Fall 2007 issue of Illumination, used a combination of laboratory experiments and computer simulations to gain insight into the notoriously opaque world of nerve-cell function and dysfunction.

Quite unexpectedly, says Schulz, they determined that neurons which appeared to work in singular ways, were, in fact, acting in a manner distinct from one another; each cell performing a unique “balancing act” that could be disrupted by disease. Schulz likes to explain it in terms of Russian literature.

“To paraphrase Leo Tolstoy, ‘Every unhappy nervous system is unhappy in its own way,’especially for individuals with epilepsy and other diseases,” he says. “Our study suggests that each patient’s neurons may be altered in different ways, although the resulting disease is the same. This could be a major reason why doctors have difficulty predicting which medicines will be effective with specific individuals. The same problem could affect treatment of heart arrhythmia, depression and many other neurological conditions.”

All neurons are biologically programmed to perform certain electric activities. If that programming is disrupted, the cell tries to restore it. Schulz’s research team, to the surprise of many in their field, observed that individual neurons appeared to be using different combinations of cellular pores, known as ion channels, to maintain and restore the same states of electrical and chemical balance.

“It’s like five people in separate rooms being given sets of blocks and told to construct a tower,” Schulz explains. Each person could devise a different method for constructing a version of what is essentially the same type of structure.

It is an insight that could have important implications in the treatment of epilepsy, he adds. Previous research has shown that neurons in the brains of epileptic patients frequently receive too little stimulation. New findings suggest that perhaps seizures might be related to under-stimulated “epileptic” neurons that are overcompensating, thus becoming too sensitive and overreacting into seizures when impulses do finally reach them. Treatments designed to stabilize such impulse imbalances warrant further study, Schulz says, “but will need to take into account the fact that compensation may differ between individuals.”

The study appeared in the June 12, 2013, issue of The Journal of Neuroscience.

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