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PMID: 10206825 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Alterations of neurotransmitter-related gene expression in human and experimental portal-systemic encephalopathy.

Metabolic brain disease ·Vol. 13 ·No. 4 ·1998-12-00 ·Pages 337-49

Butterworth RF

Abstract

Portal-systemic encephalopathy (PSE) is a serious neuropsychiatric condition that results from chronic liver failure and portal-systemic shunting of venous blood. PSE is particularly prevalent following treatment of portal hypertension or ascites by the TIPS procedure. Recent studies both in autopsied brain tissue from PSE patients as well as in experimental animal models of PSE reveal that chronic liver failure results in altered expression of several genes coding for proteins having key roles in the control of neuronal excitability. Such alterations include increased expression of monoamine oxidase (MAO-A isoform), the "peripheral-type" benzodiazepine receptor (PTBR) as well as constitutive, neuronal nitric oxide synthase (nNOS). Such changes result in altered protein expression and in increased degradation of monoamine neurotransmitters, increased synthesis of neurosteroids with inhibitory properties and increased production of nitric oxide (respectively) in brain in chronic liver failure. In the case of PTBR and nNOS, increases in expression result from exposure to ammonia and/or manganese, two neurotoxic agents shown previously to be increased in brain in chronic liver failure. Further elucidation of the consequences of neurotransmitter-related gene expression could identify new pathophysiologic mechanisms and result in new approaches to the prevention of PSE in chronic liver disease in humans.

MeSH Terms
Animals Brain/metabolism Chronic Disease Gene Expression/physiology Hepatic Encephalopathy/genetics Humans Liver Failure/genetics,metabolism Neurotoxins/metabolism Neurotransmitter Agents/genetics
Chemicals
Neurotoxins Neurotransmitter Agents
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Butterworth R F
Neuroscience Research Unit, Centre Hospitalier de l'Université de Montréal, Quebec, Canada. [email protected]
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Article Info
Journal
Metabolic brain disease
Abbr.
Metab Brain Dis
ISSN
0885-7490
DOI
10.1023/a:1020641009971
Email
[email protected]
Published
1998-12-00
Pages
337-49
Language
English
Region
United States
NLM ID
8610370
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1020641009971 View journal details
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