Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis

• Published in: Journal of hepatology Vol. 40; no. 5; pp. 742 - 748
• Main Authors: Lozeva, Violina, Montgomery, Jane A, Tuomisto, Leena, Rocheleau, Bernard, Pannunzio, Marc, Huet, Pierre-Michel, Butterworth, Roger F
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.05.2004; Elsevier
• Subjects: Aminoacid disorders; Animals; Biological and medical sciences; Brain - metabolism; Catecholamines; Constriction, Pathologic; Dopamine - metabolism; Errors of metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Hepatic Encephalopathy - etiology; Hepatic Encephalopathy - metabolism; Histamine; Histamine - metabolism; Hydroxyindoleacetic Acid - metabolism; Hyperammonemia - complications; Hyperammonemia - metabolism; Male; Medical sciences; Metabolic diseases; Norepinephrine - metabolism; Portacaval anastomosis (PCA); Portal Vein - pathology; Portasystemic Shunt, Surgical - adverse effects; Rats; Rats, Sprague-Dawley; Serotonin - metabolism; Tryptophan - metabolism; Portacaval anastomosis (PCA); Histamine; Catecholamines; Brain; Variable; Rat; Serotonin; Rodentia; Hyperammonemia; Stenosis; Catecholamine; Encephalon; Ammonia; Metabolic disorder; Vertebrata; Mammalia; Animal; Gastroenterology; Turnover; Portal vein
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2004.01.003

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. Brain monoamines have been implicated in the pathogenesis of HE. We examined the relationship between monoamine dysfunction and the degree of portal-systemic shunting (PSS) in rats with varying degrees of PSS. Concentrations of catecholamines, serotonin, histamine, precursors and metabolites in frontal cortex of rats with varying degrees of PSS (9–99.8%) were measured by HPLC. The concentrations of the serotonin precursor, tryptophan, and its metabolite, 5-HIAA were increased up to 4-fold in brains of rats with various degrees of PSS and were significantly correlated with the degree of shunting and with arterial ammonia levels. Brain levels of histamine, its precursor, l-histidine, and metabolite, tele-methylhistamine were significantly increased only following total shunting. Concentrations of catecholamines and their metabolites were not significantly correlated with degree of PSS or hyperammonemia. Given the established role of the serotonin system in the regulation of sleep, circadian rhythmicity and locomotion these findings suggest that selective alterations of this system could be implicated in the pathogenesis of HE. Therapeutic approaches aimed at the normalization of serotonin turnover could be beneficial in the prevention and treatment of early neuropsychiatric symptoms of HE.