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Related Experiment Videos

Brain indoles in human hepatic encephalopathy

H al Mardini1, E J Harrison, P G Ince

  • 1Liver Unit, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.

Hepatology (Baltimore, Md.)
|June 1, 1993
PubMed
Summary

Hepatic encephalopathy may impair consciousness due to excess serotonin (5-hydroxytryptamine) activity. This study found altered serotonin and its metabolites in the brains of patients with liver disease, particularly in the thalamus.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Hepatology

Background:

  • Serotonin (5-hydroxytryptamine) plays a key role in regulating sleep and consciousness.
  • Excess serotonin activity is hypothesized to contribute to impaired consciousness in hepatic encephalopathy (HE).
  • Elevated 5-hydroxyindoleacetic acid (5-HIAA) levels have been observed in animal models of HE.

Purpose of the Study:

  • To investigate brain levels of serotonin (5-hydroxytryptamine), its precursors, and metabolites in HE patients.
  • To correlate these neurochemical changes with the clinical condition of hepatic encephalopathy.
  • To explore the role of neurotransmitter dysregulation in HE-associated consciousness impairment.

Main Methods:

  • High-performance liquid chromatography with fluorometric detection was employed.

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  • Brain tissue from 16 HE patients (acute and chronic liver disease) and 9 controls was analyzed.
  • Levels of serotonin (5-hydroxytryptamine), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, 5-hydroxytryptophan, and indoleacetic acid were measured.

    • Main Results:

    • Significantly increased serotonin (5-hydroxytryptamine) levels were found in the thalamus of chronic HE patients.
    • Elevated levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were observed in the frontal cortex, globus pallidus, and putamen.
    • Increased levels of the precursor tryptophan and other metabolites (5-hydroxytryptophan, indoleacetic acid) were noted across various brain regions in HE patients.

    Conclusions:

    • Findings suggest disordered neurotransmission, particularly involving serotonin pathways, in hepatic encephalopathy.
    • The thalamus, crucial for consciousness regulation, shows significant alterations in serotonin levels.
    • These neurochemical changes likely contribute to the impaired consciousness observed in hepatic encephalopathy.