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Cerebral GABA-ergic and glutamatergic function in hepatic encephalopathy
Neurochemical Pathology
|February 1, 1987
Summary
Hepatic encephalopathy in chronic liver disease is linked to altered brain amino acids, specifically increased glutamine and decreased glutamate. This study suggests GABA function remains intact, but glutamate neurotransmission may be impaired.
Area of Science:
- Neuroscience
- Biochemistry
- Gastroenterology
Background:
- Hepatic encephalopathy (HE) is a complex neurological complication of chronic liver disease.
- Altered brain amino acid metabolism is implicated in HE pathogenesis.
- Previous research suggests potential neurotransmitter dysfunction in HE.
Purpose of the Study:
- To investigate amino acid changes in the brain during hepatic coma.
- To evaluate the role of GABA and glutamate in hepatic encephalopathy.
- To explore the impact of ammonia on glutamatergic neurotransmission.
Main Methods:
- Analysis of brain amino acids (glutamine, glutamate, GABA) in cirrhotic patients and animal models.
- Measurement of glutamic acid decarboxylase (GAD) activity.
- Assessment of GABA and glutamate binding to synaptic membranes.
- In vitro studies on hippocampal slices to measure glutamate release under ammonia exposure.
Main Results:
- Cirrhotic patients in hepatic coma showed increased brain glutamine and decreased glutamate.
- GABA levels and GABAergic function were unaltered in HE.
- Animal models of portal-systemic encephalopathy mirrored these amino acid changes.
- Ammonia exposure reduced glutamate release and glutamatergic neurotransmission.
- Increased [3H]glutamate binding sites were observed in hyperammonemic conditions.
Conclusions:
- Cerebral GABA function is likely not impaired in HE associated with chronic liver disease.
- A depletion of the releasable glutamate pool may contribute to HE pathophysiology.
- Neurochemical alterations in glutamate neurotransmission are significant in HE.