Experimental Study on The Alteration of Brain Cholinergic Neurotransmitter System in Hepatic Encephalopathy

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To investigate the alteration of cholinergic neurotransmitter (acethylcholine ; ACh) system in hepatic encephalopathy, we measured the concentration of choline (Ch) and ACh in six brain regions (frontal cortex, striatum, hipocampus, hypothalamus, midbrain, and medulla oblongata) in acute hepatic failure (AHF) mice induced by oral administration of thioacetamide (100mg/kg), and also evaluated these levels in the striatum of chronic hepatic failure (CHF) rat by microdialysis system in vivo. CHF with hyperammonemia was induced by porta-caval anastomosis and continuous load of ammonium acetate into caecum using osmotic pump. In AHF mice, Ch and ACh levels were significantly decreased in most brain regions, while significantly increased in monoaminergic metabolites in all brain areas. ACh levels showed a negative correlation with those of 5-HIAA.On the other hand, in CHF rat, Ch levels in the striatum were significantly decreased. But ACh levels were significantly increased. These results suggest that, although the braincholinergic neurotransmitter system is disturbed in hepatic encephalopathy, the levels of ACh may be altered due to the type of hepatic encephalopathy and blood ammonia levels. Further studies are needed to determine whether ACh is involved in the mechanism of hepatic encephalopathy.