Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures

Objective: A specific type of febrile seizure known as ‘atypical febrile seizures’ can be associated with temporal lobe epilepsy later in life. Individuals with a defect in architecture of the brain called cortical dysplasia are more susceptible to such seizures. Studies have shown a link between cortical dysplasia, the presence of atypical febrile seizures and temporal lobe epilepsy later in life, but why this is the case is not fully understood. The authors of a recent paper had developed an experimental model to study this process in rat pups (these rats are called ‘LHS rats’). Inhibitory neurotransmission in the brain is regulated by gamma amino butyric acid (GABA). GABAergic neurotransmission critically depends on the gradient of chloride inside vs. outside of neurons, and KCC2 is a chemical that regulates this gradient. In this study, the authors studied KCC2 in LHS rats to see if changes in KCC2 can cause the seizures and epilepsy.

Results: Neurons communicate with each other using electricity, and dendritic spines are small protrusions that help in transmission of electrical signals. The scientists examined dendritic spines in LHS rats and their normal counterparts in a part of the brain called the hippocampus. They found an increase in KCC2, reduced number and abnormal maturation of dendritic spines. By reducing the amount of KCC2, the scientists were able of correct deficits in dendritic spines and reduce the incidence of seizures.

Interpretation: The results suggest that an increase in KCC2 in the developing brain may lead to abnormal dendritic spines and an increase in incidence of febrile seizures.

Summary for specialists