title: Synaptic plasticity in hepatic encephalopathy - a molecular perspective.
abstract: Hepatic encephalopathy (HE)(1) is a 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.
authors.affiliation: Institute of Neural and Sensory Physiology, Medical Faculty, University of Düsseldorf D-40225 Düsseldorf, Germany.
authors.forename: Shuping
authors.initials: S
authors.lastname: Wen
authors.forename: Annett
authors.initials: A
authors.lastname: Schroeter
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Klöcker
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009473:Neuronal Plasticity; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000641:Ammonia
keywords: AMPA receptor; Functional proteomics; Hepatic encephalopathy; Membrane protein complex; NMDA receptor; Synaptic plasticity