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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lozeva
Violina
V
Neuroscience Research Unit, Hopital Saint-Luc CHUM, 1058 St-Denis St., Montreal, Que., Canada H2X 3J4.
Montgomery
Jane A
JA
Tuomisto
Leena
L
Rocheleau
Bernard
B
Pannunzio
Marc
M
Huet
Pierre-Michel
PM
Butterworth
Roger F
RF
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003251:Constriction, Pathologic; D004298:Dopamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D022124:Hyperammonemia / Q000150:complications* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011169:Portal Vein / Q000473:pathology*; D011170:Portasystemic Shunt, Surgical / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006632:Histamine; D014364:Tryptophan; D004298:Dopamine; D009638:Norepinephrine