CHAMPAIGN, Ill. (WCIA) — University of Illinois at Urbana-Champaign researchers recently discovered a compound that reduces seizures in the hippocampus, a brain region where many seizures originate.
They said the compound, known as TC-2153, lessened the severity of seizures in mice. The researchers plan to shift their focus to humans in the future.
“We found that TC-2153 ultimately reduces seizure severity in mice by decreasing the activity of hippocampal neurons,” said University of Illinois Urbana-Champaign doctoral candidate Jennifer Walters, who led the research with U. of I. molecular and integrative physiology professor Hee Jung Chung. Professor Chung is a faculty affiliate of the Beckman Institute for Advanced Science and Technology.
“In most temporal lobe epilepsy, the seizures start in the medial temporal lobe, which includes the hippocampus,” Chung said. “And 60% or more of patients who have medial temporal lobe epilepsy develop drug-resistant seizures, which correlate with the extent of neuronal death and inflammation in the hippocampus.”
According to Chung, the hippocampus plays a central role in learning and memory so anything that damages it can have devastating consequences. The strength of synaptic communication between neurons and the excitability of individual neurons can affect the likelihood that seizures occur, Chung added.
The researchers said they were surprised with the finding that TC-2153 lessened the occurrence of seizures since it is known primarily as an inhibitor of a brain-specific protein called STEP that reduces the strength of synaptic communication between neurons.
“We hypothesized that seizure activity would increase when we used TC-2153 because STEP inhibition would increase synaptic communication,” Walters said. “But we found that it actually reduced seizure severity in both male and female mice.”
Researchers discovered that the female mice responded more to treatment with the compound than the males did. To determine whether TC-2153 interacted with sex hormones, the team repeated the experiment in female mice that had their ovaries removed.
“That completely abolished the effect from the TC-2153,” Walters said. “Therefore, female sex hormones play a role in its efficacy.”
This finding may be relevant to sex differences seen in temporal lobe epilepsy, she concluded.
Follow-up experiments in mouse brains and in neuronal culture revealed a possible mechanism by which TC-2153 decreases seizure severity. The team found that the compound reduced the excitability of individual neurons, suggesting a novel function of STEP.
“TC-2153 is a STEP inhibitor,” Walters said. “So far, STEP has been known as a negative regulator of neuronal communication but was never implicated in regulating the excitability of individual neurons.”
Further studies will explore how TC-2153 works and will test its effects in human neurons, the researchers stated.
Information Credit: Diana Yates at the Illinois News Bureau.