title: Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy.
abstract: Patients with hepatic encephalopathy (HE) may present different neurological alterations including impaired cognitive function and altered motor activity and coordination. HE may lead to coma and death. Many of these neurological alterations are the consequence of altered neurotransmission. Hyperammonemia is a main contributor to the alterations in neurotransmission and in neurological functions in HE. Both glutamatergic and GABAergic neurotransmission are altered in animal models of HE. We review some of these alterations, especially those alterations in glutamatergic neurotransmission responsible for some specific neurological alterations in hyperammonemia and HE: the role 1) of excessive NMDA receptors activation in death induced by acute hyperammonemia; 2) of impaired function of the glutamate-nitric oxide-cGMP pathway, associated to NMDA receptors, in cognitive impairment in chronic HE; 3) of increased extracellular glutamate and activation of metabotropic glutamate receptors in substantia nigra in hypokinesia in chronic HE. The therapeutic implications are discussed. We also review the alterations in the function of the neuronal circuits between basal ganglia-thalamus-cortex modulating motor activity and the role of sequential alterations in glutamatergic and GABAergic neurotransmission in these alterations. HE would be a consequence of altered neuronal communication due to alterations in general neurotransmission involving different neurotransmitter systems in different neurons.
authors.affiliation: Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Avdas Autopista del Saler, 16, 46013 Valencia, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.forename: Regina
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Marta
authors.initials: M
authors.lastname: Llansola
authors.forename: Carmina
authors.initials: C
authors.lastname: Montoliu
authors.forename: Pilar
authors.initials: P
authors.lastname: Monfort
authors.forename: Blanca
authors.initials: B
authors.lastname: Piedrafita
authors.forename: Nisrin
authors.initials: N
authors.lastname: El Mlili
authors.forename: Jordi
authors.initials: J
authors.lastname: Boix
authors.forename: Ana
authors.initials: A
authors.lastname: Agustí
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid