Synaptic plasticity in hepatic encephalopathy – A molecular perspective

Hepatic encephalopathy (HE)1 iations used: Hepatic encephalopathy, HE; long-term potentiation, LTP; long-term depression, LTD; ionotropic glutamate receptors, iGluRs; AMPA receptor, AMPAR; NMDA receptor, NMDAR; Transmembrane AMPAR Regulatory Proteins, TARPs; soluble guanlyate cyclase, sGC; neuronal nitric oxide synthase, nNOS; nitric oxide, NO; reactive oxygen species, ROS; Transmembrane AMPAR Regulatory Proteins, TARPs; cornichon homologues 2 and 3, CNIH-2, CNIH-3; cystein-knot AMPAR modulating protein 44, CKAMP44; germline-specific gene 1-like protein, GSG1-like; endocytic recycling compartment, ERC. common neuropsychiatric complication of both acute and chronic liver disease. Clinical symptoms may include motor disturbances and cognitive dysfunction. Available animal models of HE mimic the deficits in cognitive performance including the impaired ability to learn and memorize information. This review explores the question how HE might affect cognitive functions at molecular levels. Both acute and chronic models of HE constrain the plasticity of glutamatergic neurotransmission. Thus, long-lasting activity-dependent changes in synaptic efficiency, known as long-term potentiation (LTP) and long-term depression (LTD) are significantly impeded. We discuss molecules and signal transduction pathways of LTP and LTD that are targeted by experimental HE, with a focus on ionotropic glutamate receptors of the AMPA-subtype. Finally, a novel strategy of functional proteomic analysis is presented, which, if applied differentially, may provide molecular insight into disease-related dysfunction of membrane protein complexes, i.e. disturbed ionotropic glutamate receptor signaling in HE.