Abstract
Childhood absence epilepsy is one of the most common paediatric epilepsies. It is characterised by frequent non-convulsive seizures causing brief loss of consciousness. Absence seizures arise within the cortico-thalamo-cortical (CTC) network; however, the precise molecular mechanisms are not fully understood and are likely multifactorial. This may account for the variability in patients' responses to antiepileptic drugs (AEDs). Although AEDs greatly improve quality of life for most patients, one third cannot be effectively treated and there is no cure for epilepsy. Understanding underlying molecular causes is imperative.
The stargazer mouse model of absence epilepsy has a mutation reducing excitatory input to feed-forward inhibitory (FFI) interneurons; FFI prevents runaway excitation in networks. The stargazer mutation specifically affects CTC parvalbumin containing GABA (γ-Aminobutyric acid) interneurons, causing FFI deficits and altered GABA levels. This study aimed to investigate whether changes in GABA levels are due to altered expression of its production enzymes, glutamate decarboxylases (GADs 65&67), and/or transport proteins, GABA transporters (GATs 1&3).