Hepatocerebral Disjunction and Brain Serotonin

Brain Tryptophan Hydroxylation in the Portacaval Shunted Rat: A Hypothesis for the Regulation of Serotonin Turnover In Vivo

“…Importantly, we used a similar PCS procedure as these authors and the results of the weight and plasma measurements were comparable between the studies (Holmin and Siesjo, 1974) and with other previous studies (Bengtsson et al, 1985(Bengtsson et al, , 1986(Bengtsson et al, , 1988Schroder et al, 1985). This indicates that the PCS rats ofthe present investigation were in a steady state of chronic PSE (for discussion see Bengtsson et al, 1989). NADH/NAD+ ratios were shown to be significantly increased in all brain regions studied (cortex, brainstem, and cerebellum) 5 weeks following PCS, which is equal to a higher degree of reduction of the cytoplasmic NADH/NAD+ system in these structures (Holmin and Siesjo, 1974).…”

“…There is a substantial body of evidence to suggest that portal-systemic encephalopathy (PSE) is associated with a significantly increased total (for overview see, e.g., Fischer and Baldessarini, 1976) and regional intraneuronal brain serotonin (5-HT) neosynthesis and turnover (for overview see, e.g., Bengtsson et al, 1989). The mechanisms underlying this increased turnover of brain 5-HT in PSE, as well as its functional relevance to serotonergic neurotransmission, however, remain obscure.…”

Brain Quinolinic Acid in Chronic Experimental Hepatic Encephalopathy: Effects of an Exogenous Ammonium Acetate Challenge

“…Increases in plasma and brain levels of L-tryptophan (L-TRP) as well as the L-TRP-derived neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) have frequently been observed in HE (e .g ., Fischer et al ., 1974 ;Mans and Hawkins, 1986 ;Bengtsson et al ., 1991) . Accordingly, interest has focused on the possible significance of a dysfunction in the serotonergic activity in the brain as a pathogenic factor in HE (for overview, see Bengtsson et al ., 1989) . Increased L-TRP levels in plasma and brain may, however, also result in an enhanced production of neurologically active metabolites other than 5-HT, one of which is quinolinic acid (QUIN ; pyridine-2,3-dicarboxylic 2235 acid) .…”

Neocortical Dialysate Monoamines of Rats After Acute, Subacute, and Chronic Liver Shunt

“…On the other hand, subacute and chronic HE/PSE resulted in significant elevations of the dialysate 5-HIAA content (and the 5-HIAA/5-HT ratio), but the extracellular 5-HT level did not appear to change per se, compared with control rats. These data may indicate that for the pathogenesis of HE a large increase in intraneuronal 5-HT biosynthesis (Bengtsson et al, 1988) does not necessarily have to correlate with, or result in, an increase in neuronal release of 5-HT in the brain, as previously suggested by the increases in the CNS tissue 5-HT metabolism in experimental HE (Cummings et al ., 1976a,b ;Mans and Hawkins, 1986; for further discussion, see also Bengtsson et al, 1989) . In fact, even a relative decrease in serotonergic tone in the CNS under some conditions of HE/PSE might be in question at least in the neocortex .…”

“…In fact, even a relative decrease in serotonergic tone in the CNS under some conditions of HE/PSE might be in question at least in the neocortex . These findings argue against a functional overactivity in the monoaminergic systems in the CNS as a direct cause of, at least, chronic HE/ PSE ; and the simplicity of the false neurotransmitter hypothesis can thus be further questioned (see also Bengtsson et al ., 1989 ;Bengtsson, 1992) .…”