Selective changes in thalamic and cortical GABA_A receptor subunits in a model of acquired absence epilepsy in the rat

Neonatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 has been shown to increase occurrence of spike-waves in EEG recordings and decrease benzodiazepines sensitivity of GABA_A receptor-mediated responses in neurons from the thalamic reticular nuclei (nRt, Wu et al., 2004). The present experiments were designed to investigate the changes in the γ2 and α1 subunits of the GABA_A receptor in CSI model rats as possible mechanisms of these changes. Western blot, immunohistochemistry and real-time PCR techniques were performed to measure the levels of GABA_A receptor γ2 and α1 subunit transcripts and protein in the nRt and ventrobasal (VB) relay nuclei of thalamus and in somatosensory cortex. In CSI model animals, Western blot results showed that γ2 subunit expression significantly decreased in thalamus (control, n = 6: 0.17 ± 0.02 relative to actin vs. CSI model, n = 6: 0.11 ± 0.01, P < 0.05) but neither in cortex nor in hippocampal tissues. Conversely, α1 subunit expression decreased in CSI model somatosensory cortex, but not in nRt and VB. The present results demonstrate that neonatal block of cholesterol synthesis produces region- and subunit-specific decreases in GABA_A receptor subunits in thalamus and cortex. Selective reductions in GABA_A receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.