Acute liver failure and hyperammonemia increase peripheral-type benzodiazepine receptor binding and pregnenolone synthesis in mouse brain

Yossef Itzhak, Ana Roig-Cantisano, Roy S. Dombro, Michael D Norenberg

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

We investigated the role of brain peripheral-type benzodiazepine receptors (PBRs) and pregnenolone (a product of PBRs activation) in hepatic encephalopathy (HE)/hyperammonemia. Administration of the hepatotoxin, thioacetamide, or ammonium acetate to mice for 3 days significantly increased the number of brain PBRs (138-146% of control) and the affinity of the ligands for these receptors (2-fold). The total content of pregnenolone and its rate of synthesis in brain of the experimental animals were significantly increased. Our results suggest a novel integrated mechanism by which ammonia-induced activation of PBRs leads to elevated levels of pregnenolone-derived neurosteroids which are known to enhance GABA-ergic neurotransmission. This mechanism may play a pivotal role in pathogenesis of HE.

Original languageEnglish
Pages (from-to)345-348
Number of pages4
JournalBrain Research
Volume705
Issue number1-2
DOIs
StatePublished - Dec 24 1995

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Keywords

  • Ammonia
  • Hepatic encephalopathy
  • Neurosteroid
  • Peripheral benzodiazepine receptor
  • Pregnenolone
  • Thioacetamide

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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