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Neurotransmitter Dysfunction in Hepatic Encephalopathy: New Approaches and New Findings

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Abstract

Hepatic Encephalopathy (HE) is a serious neuropsychiatric condition of both acute and chronic liver failure. Acute liver failure is characterized by rapid evolution of HE and by brain edema. Portal-Systemic encephalopathy (PSE) is particularly prevalent following treatment of portal hypertension or ascites by the TIPS procedure. Available evidence currently suggests that neurotransmission changes rather than brain energy failure are the primary cause of HE. Recent studies both in autopsied brain tissue from HE patients as well as in experimental animal models of HE reveal that liver failure results in altered expression of several genes coding for proteins having key roles in the control of neuronal excitability. Such alterations include decreased expression of the glutamate transporter GLT-1, and 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 extracellular brain glutamate, 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 GLT-1, PTBR, and nNOS, alterations in expression result from exposure to ammonia and/or manganese, two neurotoxic agents shown previously to be increased in brain in liver failure.

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  1. Neuroscience Research Unit, Centre Hospitalier de l', Université de Montréal (Hôpital Saint-Luc), 1058 St-Denis, Montreal, Québec, H2X 3J4, Canada

    Roger F. Butterworth

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Butterworth, R.F. Neurotransmitter Dysfunction in Hepatic Encephalopathy: New Approaches and New Findings. Metab Brain Dis 16, 55–65 (2001). https://doi.org/10.1023/A:1011614528751

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