Developmental Inhibitory Changes in the Primary Somatosensory Cortex of the Stargazer Mouse Model of Absence Epilepsy

Childhood absence epilepsy seizures arise in the cortico-thalamocortical network due to multiple cellular and molecular mechanisms, which are still under investigation. Understanding the precise mechanisms is imperative given that treatment fails in similar to 30% of patients while adverse neurological sequelae remain common. Impaired GABAergic neurotransmission is commonly reported in research models investigating these mechanisms. Recently, we reported a region-specific reduction in the whole-tissue and synaptic GABA(A) receptor (GABA(A)R) alpha 1 subunit and an increase in whole-tissue GAD65 in the primary somatosensory cortex (SoCx) of the adult epileptic stargazer mouse compared with its non-epileptic (NE) littermate. The current study investigated whether these changes occurred prior to the onset of seizures on postnatal days (PN) 17-18, suggesting a causative role. Synaptic and cytosolic fractions were biochemically isolated from primary SoCx lysates followed by semiquantitative Western blot analyses for GABA(A)R alpha 1 and GAD65. We found no significant changes in synaptic GABA(A)R alpha 1 and cytosolic GAD65 in the primary SoCx of the stargazer mice at the critical developmental stages of PN 7-9, 13-15, and 17-18. This indicates that altered levels of GABA(A)R alpha 1 and GAD65 in adult mice do not directly contribute to the initial onset of absence seizures but are a later consequence of seizure activity.

Automated summary

Childhood absence epilepsy seizures arise from multiple cellular and molecular mechanisms in the cortico-thalamocortical network, which are still being investigated. Understanding these mechanisms is crucial due to the high treatment failure rate and common adverse neurological sequelae.