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 language | English (US) |
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Pages (from-to) | 345-348 |
Number of pages | 4 |
Journal | Brain research |
Volume | 705 |
Issue number | 1-2 |
DOIs | |
State | Published - Dec 24 1995 |
Keywords
- Ammonia
- Hepatic encephalopathy
- Neurosteroid
- Peripheral benzodiazepine receptor
- Pregnenolone
- Thioacetamide
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- Neuroscience(all)