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09-06-2015 | New research identifies the cause of memory loss in those with temporal lobe epilepsy

09 June 2015
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Researchers at the University of Alabama at Birmingham (UAB) have identified why individuals with temporal lobe epilepsy (TLE) are prone to memory loss, and suggest possible means of reversing this loss. There are indications that the UAB findings may have implications for many other memory conditions.

Individuals with temporal lobe epilepsy have an above average occurrence of memory loss, even when their epilepsy is well controlled by the use of medication. The UAB research team targeted on the brain-derived neurotrophic factor (BDNF) gene, which is important for long-term memory, and is known to be a factor in memory formation.

A study of external or environmental factors that turn genes on and off and affect how cells read genes called DNA methylation regulates were undertaken. When turned on, a gene transmits instructions for the production of its particular protein. When turned off, production of that protein stops. Disruptions in DNA methylation can affect whether a gene is on or off, with a corresponding change in the amount of protein produced.

Individuals with temporal lobe epilepsy experience a decrease in DNA methylation at the BDNF gene, which stops the BDNF gene from turning off at the right time, said the study's lead investigator, Farah Lubin, Ph.D., an assistant professor in the Department of Neurobiology, UAB.

"This leads to increased gene expression and elevated amounts of messenger RNA, which transmits the gene's instructions to the brain," Lubin said. "This results in an over-expression of the BDNF protein, which appears to severely compromise normal memory formation in patients with temporal lobe epilepsy."

The study was conducted in a rat model for temporal lobe epilepsy; Lubin says that boosting DNA methylation reduced the amount of mRNA and the amount of BDNF protein, restoring more typical memory function. Lubin's team used an amino acid called methionine, available as a dietary supplement, to increase DNA methylation in the epileptic rat brain.

"What is exciting is that this is the first time we've been able to reverse memory deficits in this patient population through a better understanding of DNA methylation," Lubin said. "This could have ramifications for a number of other memory disorders, including Alzheimer's disease or other forms of dementia. This could also be very important for children with epilepsy, as our findings suggest for the first time that memory loss due to epilepsy may be reversible."

Lubin says that a great deal of what science knows regarding memory formation and loss can be credited to knowledge gained in the study of epilepsy.

Lubin says it is fitting that the current study may ultimately benefit patients with epilepsy; although she cautions that methionine's effects on memory formation in humans still requires further study.

Lubin says the next steps are to conduct similar DNA methylation studies on other genes known to be a factor in memory formation. New technologies allow researchers to do what is called gene editing, a kind of genetic engineering in which DNA is added, removed or altered in a genome. This allows researchers to better understand the function of a gene or the protein it produces by manipulating DNA methylation levels at the single gene and monitoring its effects on the organism.

Prof. Lubin has received a grant from the National Institute of Neurological Disorders and Stroke which will fund further studies.

Source:  UAB News, June 05, 2015

Published: Annals of Translational and Clinical Neurology, Article first published online: 12 MAR 2015, DOI: 10.1002/acn3.183

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