Abnormalities in brain serotonin concentration, high-affinity uptake, and tryptophan hydroxylase activity in severe-seizure genetically epilepsy-prone rats

Epilepsia
M A StatnickR A Browning

Abstract

We characterized the nature of the deficit in brain serotonin (5-HT) exhibited by genetically epilepsy-prone rats (GEPR-9s) by regionally assessing three markers for 5-HT terminals/neurons (5-HT content, 5-HT uptake into the P2-synaptosomal fraction, and tryptophan hydroxylase activity) in GEPR-9s and nonepileptic control rats. As compared with controls, GEPR-9s had reduced brain 5-HT concentration, synaptosomal 5-HT uptake, and tryptophan hydroxylase activity (measured in vivo and in vitro) in most regions of the forebrain and in selected regions of brainstem. Analysis of kinetic constants for synaptosomal [(3)H]5-HT uptake and in vitro tryptophan hydroxylase activity showed that the decrements in these parameters exhibited by GEPR-9s resulted from reductions in V(max) rather than changes in K(m). In general, the reduction in each of the presynaptic markers for 5-HT terminals/neurons was similar in both magnitude and in their regional distribution in the GEPR-9 brain. An exception to this was noted in the midbrain tegmentum of GEPR-9s, which displayed a significant reduction in tryptophan hydroxylase activity without showing alterations in 5-HT concentration or in high-affinity 5-HT uptake. The present findings support the hyp...Continue Reading

References

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Citations

Nov 11, 1998·European Journal of Pharmacology·E SouthamR M Hagan
Apr 6, 2001·Neurochemistry International·J FilakovszkyG Bagdy
Oct 6, 2001·Pediatric Neurology·A Di Martino, R F Tuchman
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Sep 4, 2012·Biochemical Pharmacology·S Alisha Epps, David Weinshenker
Jul 3, 2016·Cold Spring Harbor Perspectives in Medicine·Andrey Mazarati, Raman Sankar
Nov 29, 2016·Frontiers in Neuroscience·Dubravka Svob StracGiuseppe Di Giovanni
Dec 24, 2019·Experimental Neurology·Alexandra N PetrucciGordon F Buchanan

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