Abstract
The research reported here has been done on a mutant stain of Fayoumi fowl having a hereditary form of primary generalized epilepsy. Heterozygotes do not have seizures and were used as age-matched controls. The hypothesis is that the low seizure threshold in epileptic fowl is due to increased neuronal nitric oxide synthase (nNOS) activity in the forebrain region of these animals and to explore the possible causes of the abnormal nNOS activity. Results reported here demonstrated that nNOS activity in epileptic fowl forebrain increased significantly when compared to age-matched carrier chicks. Both epileptic and carrier chicks displayed an increase in forebrain nNOS activity during postnatal development. A single dose injection with the selective nNOS inhibitor, 7-nitroindazole (7-NI), reduced nNOS activity and the seizure severity in animals exposed to IPS. The levels of nNOS protein were examined by western blot analysis. Epileptic chickens had the same amount nNOS protein as did age-matched carriers and normal chicks. Furthermore, in addition to an expected 10 kbp mRNA, a shorter mRNA was also detected in epileptic chickens perhaps indicating an in-frame deletion in the nNOS gene. In vitro investigate and compare the concentration-dependent inhibition of 2-Thiouracil(TU) on nNOS activity in forebrain extracts from both epileptic and carrier fowl to determine if structural differences may exist in the nNOS enzyme. TU inhibition of nNOS activity was concentration-dependent, and at high concentrations of TU the inhibition was statistically significant between epileptic and carrier fowl. Furthermore, the different inhibition pattern of TU suggests the possibility that nNOS in the epileptic animals is structurally different from carrier enzyme. The data indicates that nNOS is involved in the low seizure threshold in this animal model.
Published Version
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