Experimentally induced attenuation of neuropeptide-Y gene expression in transgenic mice increases mortality rate following seizures

Previous experiments have reported increased seizure susceptibility in tran sgenic mice lacking normal neuropeptide-Y (NPY) gene expression (i.e. NPY ' knock-out' mice). A critical issue inherent in such experiments concerns th e confounding of developmental influences of NPY and its neurotransmitter f unctions in the mature organism. The present experiments directly addressed this issue by studying seizure susceptibility in transgenic mice possessin g an inducible antisense transcript that can be experimentally manipulated to attenuate NPY synthesis. NPY-deficient and control mice were injected wi th kainic acid (40 mg/kg, i.p.) and several seizure-related behaviors were measured. Consistent with previously reported effects in NPY knock-out mice , significantly more NPY-deficient mice died within 24 h than control mice. In situ hybridization analyses confirmed a decrease in prepro-NPY gene exp ression in transgenic mice. The experiments support the hypothesis that the control of neural excitability is a prominent function of NPY. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.