Portal-systemic encephalopathy: a disorder of neuron-astrocytic metabolic trafficking.
Portal-systemic encephalopathy (PSE) is a major neuropsychiatric complication of chronic liver disease. Neuropathologic evaluation of brain tissue from cirrhotic patients who died in hepatic coma reveals astrocytic (rather than neuronal) changes referred to as Alzheimer type II astrocytosis. Evidence to date suggests that Alzheimer type II astrocytosis is the result of ammonia neurotoxicity. Exposure of cultured astrocytes to concentrations of ammonia equivalent to those encountered in brain in experimental PSE results in Alzheimer type II astrocytosis as well as changes in other astrocytic parameters such as glial fibrillary acidic protein and glycogen metabolism. A second characteristic of PSE is the appearance of increased densities of 'peripheral-type' benzodiazepine receptors (PTBRs) in both brain and peripheral tissues. In brain, PTBRs are highly localized on astrocytic outer mitochondrial membranes. Experimental PSE resulting from portacaval anastomosis in the rat results in increased densities of PTBRs in brain and in increased expression of the endogenous PTBR ligand octadecaneuropeptide in nonneuronal elements. It is suggested that the PTBR and its endogenous ligands could mediate the astrocytic response to chronic exposure to ammonia in PSE. Astrocytic changes in PSE are accompanied by disruption of neuron-astrocytic metabolic trafficking. In particular, reuptake of the neurotransmitter glutamate into the perineuronal astrocyte is inhibited in PSE resulting in glutamatergic synaptic dysregulation and potentially compromised astrocytic energy metabolism. Astrocytic metabolism of monoamine neurotransmitters may also be increased as a result of increased activities of monoamine oxidase MAOB.
Butterworth
R F
RF
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Que, Canada.
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism*