Activation of the GABA(A)-receptor δ-subunit gene promoter following pentylenetetrazole-induced seizures in transgenic mice

Silke Penschuck, Bernhard Lüscher, Jean Marc Fritschy, Florence Crestani

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

An impairment of GABA(A)-receptor-mediated inhibitory neurotransmission has been implicated in the development of epileptic seizures. To determine whether seizures affect GABA(A)-receptor gene transcription in vivo, a transgenic mouse line carrying a lacZ-fusion gene driven by GABA(A)-receptor δ-subunit promoter and upstream sequences was subjected to pentylenetetrazol (PTZ)-induced seizures. After injection of a single convulsive dose of PTZ, the activity of the δ-subunit promoter, as monitored by β-galactosidase immunohistochemistry, was increased selectively in neurons of layers II-IV of neocortex. In contrast, mice kindled by repeated administration of initially subconvulsive doses of PTZ did not show a change in transgene expression, even shortly after the last PTZ-induced seizure. These results show that transient changes in transcription of the GABA(A)-receptor δ-subunit gene occur after acute seizures, but not after kindling. The limited responsiveness of the GABA(A)-receptor δ-subunit promoter after repeated stimulation may reflect an inappropriate adaptation of cellular responses to recurrent excitation, thereby contributing to the development of seizure.

Original languageEnglish (US)
Pages (from-to)212-219
Number of pages8
JournalMolecular Brain Research
Volume51
Issue number1-2
DOIs
StatePublished - Nov 1 1997

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Activation of the GABA(A)-receptor δ-subunit gene promoter following pentylenetetrazole-induced seizures in transgenic mice'. Together they form a unique fingerprint.

  • Cite this