DURHAM, N.C. -- While epilepsy has long been thought to boost production of new brain cells (neurons) as a means of repairing injury, a new study shows that chronic seizures actually decrease new neuron production in the brain's learning and memory center.
The study is the first to demonstrate how new neuron production in the brain's "hippocampus" is affected by chronic, rather than acute, seizures, said the researchers from Duke University Medical Center and the Durham VA Medical Center. The hippocampus is the brain region where learning, memory and mood are regulated and where epilepsy causes injury.
In the study, rats with chronic epilepsy showed a 75 percent decrease in new neuron production in the hippocampus compared to normal animals, said Ashok K. Shetty, Ph.D., a research professor of neurosurgery at Duke and the study's senior author.
The finding explains why chronic epileptics are prone to learning and memory deficits and depression, he said. Epilepsy occurs when electrical signals in the brain are disrupted, causing uncontrolled body movements and changes in learning, memory and emotion.
Shetty said their new knowledge of neuron growth, or neurogenesis, in chronic epilepsy could lead to treatments that alleviate the learning and memory deficits and mood symptoms that accompany the disease. The findings could potentially even reduce the prevalence of seizures, he said.Results of their study on neurogenesis in rats with epileptic seizures are published in the December issue of Neurobiology of Disease. Bharathi Hattiangady, Ph.D., research associate in neurosurgery, is the lead author, and research associate Muddanna Rao, Ph.D., is co-author of the study. The study is funded the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health.
"In the future, we could theoretically treat chronically epileptic patients with stem cell factors that induce new neuron production and see if it alleviates their learning and memory problems and depression; or we could prescribe exercise, enriched environment or anti-depressants," said Shetty. "All of these treatments are known to considerably increase adult neurogenesis in the hippocampus where learning, memory and mood are regulated."
In the Duke study, rats were induced to have seizures and hippocampal injury analogous to humans with temporal lobe epilepsy – the most common form of epilepsy. Immediately following the acute seizures, there was a 60 percent increase in new neuron production in the brain's hippocampus. A respite period with no seizures lasted for four to six weeks, and then seizures recurred with increasing severity – the chronic phase of temporal lobe epilepsy. During the chronic phase, rats displayed an average 75 percent decrease in neurogenesis compared with normal rats.
The more frequent the rats' seizures were, the fewer new neurons they produced in the long term, the study showed. And, the fewer neurons their brains produced, the more likely they were to suffer more seizures."With chronic epilepsy, the brain's wiring is reorganized to become more excitable," said Shetty. "The seizures induce changes in nerve cells that make them more susceptible to additional seizures."
The rapid production of new nerve cells following acute seizures was thought to repair damage, said Shetty. But the Duke study, as well as earlier studies, indicate that such rapid neurogenesis actually dispatches neurons to the wrong places and contributes to abnormal brain circuitry and hyper-excitability of neurons. Moreover, the delicate balance between excitatory neurons that fire signals and inhibitory neurons which halt them is lost, tipping the balance toward hyper-excitability.
"Studying early time-points in the epileptic brain produces an entirely different picture than studying the long-term effects of chronic seizures," said Shetty. "Understanding the brain's long-term response to epileptic injury will enhance our ability to treat the disease," he added.
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