Alterations of neurotransmitter-related gene expression in human and experimental portal-systemic encephalopathy.
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.
Butterworth
R F
RF
Neuroscience Research Unit, Centre Hospitalier de l'Université de Montréal, Quebec, Canada. butterwr@ere.umontreal.ca
D000818:Animals; D001921:Brain / Q000378:metabolism; D002908:Chronic Disease; D015870:Gene Expression / Q000502:physiology*; D006501:Hepatic Encephalopathy / Q000235:genetics*; D006801:Humans; D017093:Liver Failure / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000235:genetics*
D009498:Neurotoxins; D018377:Neurotransmitter Agents