Neurotransmitter receptor alterations in hepatic encephalopathy: A review

Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome with symptoms ranging from subtle neuropsychiatric and motor disturbances to deep coma and death, is thought to be a clinical manifestation of a low-grade cerebral oedema associated with an altered neuron-astrocyte crosstalk and exacerbated by hyperammonemia and oxidative stress. These events are tightly coupled with alterations in neurotransmission, either in a causal or a causative manner, resulting in a net increase of inhibitory neurotransmission. Therefore, research focussed mainly on the potential role of gamma-aminobutyric acid-(GABA) or glutamate-mediated neurotransmission in the pathophysiology of HE, though roles for other neuro-transmitters (e.g. serotonin, dopamine, adenosine and histamine) or for neurosteroids or endogenous benzodiazepines have also been suggested. Therefore, we here review HE-related alterations in neuro-transmission, focussing on changes in the levels of classical neurotransmitters and the neuromodulator adenosine, variations in the activity and/or concentrations of key enzymes involved in their metabolism, as well as in the densities of their receptors. (C) 2013 Elsevier Inc. All rights reserved.