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

Huifang Li, Alli Kraus, Jie Wu, John R. Huguenard, Robert S. Fisher

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 GABAA 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 GABAA 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 GABAA 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 GABAA receptor subunits in thalamus and cortex. Selective reductions in GABAA receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.

Original languageEnglish (US)
Pages (from-to)121-128
Number of pages8
JournalNeuropharmacology
Volume51
Issue number1
DOIs
StatePublished - Jul 2006
Externally publishedYes

Keywords

  • Absence epilepsy
  • Cholesterol synthesis inhibitor
  • GABA receptor subunit
  • Somatosensory cortex
  • Thalamic reticular nucleus
  • Ventrobasal relay nucleus

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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