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Fragile period of childhood brain development could underlie epilepsy
Date:8/23/2009

BOSTON A form of partial epilepsy associated with auditory and other sensory hallucinations has been linked to the disruption of brain development during early childhood, according to a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC).

Described in today's Advance On-line issue of Nature Medicine, these new findings provide the first genetic link between childhood brain development and a seizure disorder that lasts throughout adulthood, and also identify a new pathway that controls how neuron circuits are "pruned" and matured.

"During early childhood roughly between the ages of one and five the brain undergoes a period of major circuit remodeling," explains senior author Matthew Anderson, MD, PhD, a principal investigator in the Departments of Neurology and Pathology at BIDMC. "Our discovery that a familial form of temporal lobe epilepsy can develop at this point demonstrates the fragility of the brain during this critical period."

The new findings focus on the development of synapses, the connections between brain cells.

"At birth, the brain is loaded with excitatory synapses which help make nerve cells 'fire,'" explains Anderson, who is also an Assistant Professor of Neurology and Pathology at Harvard Medical School. "However, if these excess synapses are not adequately 'pruned,' they can overgrow, leading to excessive transmission of excitatory signals and the development of pathological conditions, including learning disabilities and autism in addition to epilepsy."

Using a genetically engineered mouse model created in his laboratory, together with brain slice patch-clamp electrophysiology techniques, Anderson and his scientific team found that a mutant form of the LGI1 (leucine-rich glioma-inactivated 1) gene was preventing the normal brain development.

"The first clue was our discovery that LGI1 is not expressed until the exact time when excitatory synapses are matured
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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