The link between a therapeutic drug and a neural protein involved in epilepsy
by Brittany Mier
Epilepsy is a neurological disorder that affects the brain and manifests itself in the form of seizures. These seizures occur when brain tissue emits an abnormal electrical discharge which may result in abnormal body movement or behavior. In a recent study published in the Journal of Neuroscience, Dr. John Huguenard, Director of the Stanford Neuroscience Graduate Program, and lead author and postdoctoral scholar Julia Brill shed light on the underlying mechanisms behind an epilepsy therapeutic called valproic acid (VPA).
A new understanding of the traditional treatment for epilepsy
VPA has been previously used to treat epilepsy, but its mechanism of action has never been fully understood. Huguenard and Brill discovered that VPA may work to increase the concentration of neuropeptide Y (NPY) in certain parts of the brain. A naturally occurring anti-convulsant that also regulates feeding, memory, and learning, NPY is a 36 amino acid neurotransmitter found in the brain and autonomic nervous system.
When VPA is administered to rats, researchers found that the levels of NPY in the thalamus and hippocampus increased by about 50%. Amazingly, these two parts of the brain are the areas associated with petit mal and temporal lobe epileptic seizures. This finding suggested a reason for the anti-epileptic action of VPA, and also shed light on a possible way for the brain to suppress seizures: stimulate the neurons to produce more NPY. ÒUnfortunately,Ó Professor Huguenard explains, Òthere arenÕt very many neurons that produce NPY naturally in the brain. They only make up about 5% of the neuron population.Ó However, increasing NPY production with VPA administration could have significant therapeutic benefits for epilepsy.
How does VPA work to control seizures?
Normally, when a person has a seizure, the abnormal activity begins in one region of the brain and then spreads quickly throughout the rest of the brain, causing all of the affected neurons to react in synchronization. The convulsions associated with seizures are a direct product of this synchronized activity While abnormal electrical activity in the brain may still exist after VPA administration, the extra concentration of NPY will keep it isolated in the region of the brain where it initially started before it spreads to the rest of the brain.
Future possibilities for epilepsy patients
In the near future, stem cells may be used to cultivate extra NPY-producing neurons to be injected directly into the brain. Scientists may also figure out how to trigger the brain to produce more NPY on its own, without the help of VPA or other prescription drugs. Either way, potential treatments for patients suffering from epilepsy are promising.