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Probing the nucleus of focal epilepsy.

Probing the nucleus of focal epilepsy

Scientists have detected chromosomal rearrangements inside certain brain cells of epileptic patients, a finding that could help explain why these cells can initiate recurrent seizures, they report in the Dec. 23 SCIENCE.

Focal epilepsy--seizures arising from a specific population of brain cells--can be due to a turmo or scar from a recent injury, but sometimes these seizures begin for no apparent reason. Physicians often attribute such surprising seizures to a much earlier damaging event, such as an automobile accident or even birth trauma, that produced a sort of latent cecebral "spark" that now "kindles" recurrent seizures in other brain cells.

Scientists have studied particular genes and neurotransmitters associated with seizure activity as well as longer-lasting changes within epileptic cells or their membranes. Until recently, however, no one had looked at the chromosomal changes that might underlie a cell's "long-term memory" for repeatedly recalling epileptic attacks, says study leader Lara Manuelidis, a neuropathologist at Yale University School of Medicine.

Manuelidis and medical intern Jonathan Borden at Tufts New England Medical Center in Boston studied in detail the nuclei of epileptic and normal cells sampled (initially for diagnostic purposes) from the cerebral cortex of five patients suffering from recurrent epileptic seizures.

To examine the overall arrangement and stucture of genetic material inside the nuclei, the researchers used molecular probes that attach to and color specific chromosomal regions. With this method, they highlighted for individual chromosomes in normal and seizure-provoking cells.

Although three of the studied chromosomes appeared in their normal nuclear location in all tissue samples, the X chromosome in male tissue and at least one of the X chromosomes in female tissue appeared in a distinct location within the nuclei of seizure-initiating cells. The repositioned X chromosomes were also more extended than the X chromosomes from normal tissue, indicating their genes may be more active.

The researchers propose that some initially asymptomatic event causes a "more or less" permanent rearrangement of specific chromosomes, including the X, in certain brain cells and that this rearragment enables the cells to electricity ignite uncontrollable, spreading epileptic seizures.
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Author:Wickelgren, Ingrid
Publication:Science News
Date:Dec 24, 1988
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