Seizure Severity in Mice Is Surprisingly Silenced by Compound

Seizure Severity in Mice Is Surprisingly Silenced by Compound ...

Researchers studying epileptic seizures of the temporal lobe the most common type of epilepsy discovered a compound that reduces seizures in the hippocampus, a brain area where many such seizures originate. The compound, known as TC-2153, reduced the severity of seizures in mice.

In the journalEpilepsia, the scientists analyze their findings.

We found that TC-2153 reduced seizure severity in mice by reducing the activity of hippocampal neurons, according to the University of Illinois Urbana-Champaign doctoral candidate. Walters, who led the research with the United States of America''s Molecular and integrative physiologyprofessor, said.

Chung said that the seizures in the medial temporal lobe begin in the hippocampus. In most patients with medial temporal lobe epilepsy, 60% or more have developed drug-resistant seizures, which are linked to the extent of neuronal death and inflammation in the hippocampus.

She believes that the hippocampus plays a major role in learning and memory, so that any damage it may have catastrophic consequences for the individual.

Chung said the strength of synaptic communication between neurons and the excitability of each individual neurons may have an influence on the likelihood that seizures occur.

The conclusion that TC-2153 decreased the number of seizures was a surprise, according to the researchers, because it is primarily an inhibitor of a brain-specific protein called STEP that reduces the strength of synaptic communication between neurons.

Because of STEP inhibition, Walters said, seizure severity was reduced in male and female mice.

Female mice responded more to treatment with the compound than males did. The researchers repeated an experiment in female mice with their ovaries to determine whether TC-2153 interacted with sexual hormones.

Walters said the TC-2153 had completely abolished the effects. Female sex hormones play a role in its effectiveness. This finding may be related to sex differences observed in temporal lobe epilepsy, she said.

Follow-up experiments in mouse brains and neuronal culture revealed a mechanism by which TC-2153 decreases seizure severity. According to Chung, the compound reduced the excitability of individual neurons, suggesting a novel function of STEP.

TC-2153 is a STEP antagonist, according to the author. So far, STEP has been described as a negative regulator of neuronal communication, but was never implicated in regulating individual neurons'' excitability.

According to researchers, further research will investigate how TC-2153 works and how it might affect human neurons.

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