The epilepsies are a group of neurological disorders associated with recurring seizures that tend to become more frequent and severe over time.
Adenosine decreases neuronal excitability and helps stop seizures. Earlier studies have suggested abnormally low levels of adenosine may be linked to epilepsy.
Rebecca L Williams-Karnesky, and her colleagues from Legacy Research Institute, Portland, Oregon Health and Sciences University (OHSU), Portland, and Tufts University, Boston, looked at long-term effects of an adenosine-releasing silk-implant therapy in rats.
They found that adenosine's beneficial effects are due to epigenetic modifications (chemical reactions that change the way genes are turned on or off without altering the DNA code, the letters that make up our genetic background).
Specifically, these changes happen when a molecule known as a methyl group blocks a portion of DNA, affecting which genes are accessible and can be turned on. If methyl groups have been taken away (demethylated), genes are more likely to turn on.
Researchers found evidence that changing adenosine levels affects DNA methylation in the brain. Specifically, greater amounts of adenosine were associated with lower levels of DNA methylation.
Epileptic rat brains that had received the adenosine-releasing silk implants exhibited DNA methylation levels close to brains of normal rats and this significantly lessened the worsening of the epilepsy over time.
One mechanism involved in a specific type of epilepsy is an increase in mossy fibre sprouting - the formation of new excitatory circuits in the part of the brain where seizures commonly originate.
At the end of the experiment, animals that had been treated with the adenosine-releasing silk implant showed less sprouting than animals that were not given the drug.
The findings show that the implants are safe to use in rats and suggest that they may one day be used in the clinic, the study said.
The research was published in the Journal of Clinical Investigation.
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