Deficit of endogenous kynurenic acid in the frontal cortex of rats with a genetic form of absence epilepsy.
The present studies sought to determine the concentrations of endogenous kynurenic acid (KYNA) and to measure the activity of kynurenine aminotransferases (KAT) I and II in the discrete brain regions of 3- and 6-month old WAG/Rij rats, a genetic model of absence epilepsy. Analogues experiments were performed using age-matched ACI rats, which served as a non-epileptic control. The age-dependent increase in KYNA concentration in the frontal cortex of WAG/Rij rats was considerably reduced in comparison to what was found in ACI rats. Consequently, the concentration of KYNA in the frontal cortex of epileptic rats was significantly lower than in non-epileptic controls. There were no such strain differences in other brain regions. The activities of KAT I and II also showed age-dependent increase with an exception for KAT II in the frontal cortex. Our data suggest that selective deficits of endogenous KYNA may account for increased excitability in the frontal cortex, which in turn may lead to the development of spontaneous spike-wave discharges in WAG/Rij rats.
Kamiński
Rafał M
RM
Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, PL 20-950 Lublin, Poland.
Zielińska
Elzbieta
E
Dekundy
Andrzej
A
van Luijtelaar
Gilles
G
Turski
Waldemar
W
D000375:Aging / Q000502:physiology; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D003342:Corpus Striatum / Q000737:chemistry; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics*; D005625:Frontal Lobe / Q000737:chemistry* / Q000201:enzymology / Q000503:physiopathology; D007736:Kynurenic Acid / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D007737:Kynurenine; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D013787:Thalamic Nuclei / Q000737:chemistry / Q000201:enzymology; D000637:Transaminases / Q000737:chemistry / Q000378:metabolism
D007737:Kynurenine; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D007736:Kynurenic Acid