title: Experimentally induced attenuation of neuropeptide-Y gene expression in transgenic mice increases mortality rate following seizures.
abstract: Previous experiments have reported increased seizure susceptibility in transgenic mice lacking normal neuropeptide-Y (NPY) gene expression (i.e. NPY 'knock-out' mice). A critical issue inherent in such experiments concerns the confounding of developmental influences of NPY and its neurotransmitter functions in the mature organism. The present experiments directly addressed this issue by studying seizure susceptibility in transgenic mice possessing an inducible antisense transcript that can be experimentally manipulated to attenuate NPY synthesis. NPY-deficient and control mice were injected with 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 expression in transgenic mice. The experiments support the hypothesis that the control of neural excitability is a prominent function of NPY.
authors.affiliation: Department of Psychology, The University of Georgia, Athens, GA 30602, USA.
authors.forename: S
authors.initials: S
authors.lastname: DePrato Primeaux
authors.forename: P V
authors.initials: PV
authors.lastname: Holmes
authors.forename: R J
authors.initials: RJ
authors.lastname: Martin
authors.forename: R G
authors.initials: RG
authors.lastname: Dean
authors.forename: G L
authors.initials: GL
authors.lastname: Edwards
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000009:adverse effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000172:deficiency* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000401:mortality* / Q000503:physiopathology*
chemical_list: D009478:Neuropeptide Y; D012333:RNA, Messenger; D007608:Kainic Acid