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Metabolic Brain Disease

, Volume 24, Issue 1, pp 69–80 | Cite as

Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy

  • Omar Cauli
  • Regina Rodrigo
  • Marta Llansola
  • Carmina Montoliu
  • Pilar Monfort
  • Blanca Piedrafita
  • Nisrin el Mlili
  • Jordi Boix
  • Ana Agustí
  • Vicente FelipoEmail author
Original Paper

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.

Keywords

Hepatic encephalopathy Glutamate GABA Hypokinesia Motor function Neuronal circuits Hyperammonemia 

Notes

Acknowledgements

This work was supported by grants from Ministerio de Educación y Ciencia (SAF2005-06089) and from Ministerio de Sanidad (Red G03-155 and FIS PI050253) of Spain and from Consellería de Empresa, Universidad y Ciencia (GV04B-012, GVS05/082, ACOMP06/005; ACOMP/2007/002) and AP005/06 and EVES 034/2007 from Conselleria de Sanitat, Generalitat Valenciana

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Omar Cauli
    • 1
  • Regina Rodrigo
    • 1
  • Marta Llansola
    • 1
  • Carmina Montoliu
    • 1
  • Pilar Monfort
    • 1
  • Blanca Piedrafita
    • 1
  • Nisrin el Mlili
    • 1
  • Jordi Boix
    • 1
  • Ana Agustí
    • 1
  • Vicente Felipo
    • 1
  1. 1.Laboratory of NeurobiologyCentro de Investigacion Principe FelipeValenciaSpain

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