Home LiteratureArticle Details
PMID: 9364040 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Knock-out mice reveal a critical antiepileptic role for neuropeptide Y.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 17 ·No. 23 ·1997-12-01 ·Pages 8927-36

Baraban SC, Hollopeter G, Erickson JC, Schwartzkroin PA, Palmiter RD

Abstract

Neuropeptide Y (NPY) inhibits excitatory synaptic transmission in the hippocampus and is implicated in control of limbic seizures. In the present study, we examined hippocampal function and the response to pharmacologically induced seizures in mutant mice lacking this peptide. In slice electrophysiology studies, no change in normal hippocampal function was observed in NPY-deficient mice compared with normal wild-type littermates. Kainic acid (KA) produced limbic seizures at a comparable latency and concentration in NPY-deficient mice compared with littermates. However, KA-induced seizures progressed uncontrollably and ultimately produced death in 93% of NPY-deficient mice, whereas death was rarely observed in wild-type littermates. Intracerebroventricular NPY infusion, before KA administration, prevented death in NPY-deficient mice. These results suggest a critical role for endogenous NPY in seizure control.

MeSH Terms
Action Potentials/drug effects Animals Convulsants/toxicity Electroencephalography Epilepsy/physiopathology Gene Expression Regulation/drug effects Genotype Hippocampus/drug effects,physiology Kainic Acid/toxicity Mice Mice, Knockout Neuropeptide Y/biosynthesis,deficiency,genetics,physiology,therapeutic use Perforant Pathway/drug effects,physiopathology Seizures/chemically induced,physiopathology,prevention & control Synaptic Transmission/drug effects,physiology
Chemicals
Convulsants Neuropeptide Y Kainic Acid
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Baraban S C
Department of Neurological Surgery, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Hollopeter G
Erickson J C
Schwartzkroin P A
Palmiter R D
References (51)
51 references, click to expand
  1. Mesial temporal lobe epilepsy: clinical features and seizure mechanism.
    Epilepsia. 1996;37 Suppl 3:57-60 PMID: 8681916
  2. An intracellular study of dentate, CA1 and CA3 neurones in the mouse hippocampal slice.
    Q J Exp Physiol. 1985 Apr;70(2):189-202 PMID: 4011835
  3. Neuropeptide Y inhibits hippocampal seizures and wet dog shakes.
    Brain Res. 1996 Oct 21;737(1-2):162-8 PMID: 8930362
  4. Differential NPY mRNA expression in granule cells and interneurons of the rat dentate gyrus after kainic acid injection.
    Hippocampus. 1994 Aug;4(4):474-82 PMID: 7874238
  5. Differential increases in brain levels of neuropeptide Y and vasoactive intestinal polypeptide after kainic acid-induced seizures in the rat.
    Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):173-7 PMID: 2566924
  6. Paired-pulse facilitation and inhibition in the dentate gyrus is dependent on behavioral state.
    Exp Brain Res. 1989;77(3):594-604 PMID: 2806450
  7. The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice.
    Neuron. 1991 Nov;7(5):703-16 PMID: 1742021
  8. Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after intermittent excitatory stimulation in adult rat hippocampus in vivo.
    J Comp Neurol. 1996 Mar 25;367(1):132-46 PMID: 8867287
  9. Regional distribution of putative NPY Y1 receptors and neurons expressing Y1 mRNA in forebrain areas of the rat central nervous system.
    Eur J Neurosci. 1993 Dec 1;5(12):1622-37 PMID: 8124516
  10. Action and location of neuropeptide tyrosine (Y) on hippocampal neurons of the rat in slice preparations.
    J Comp Neurol. 1987 Mar 8;257(2):208-15 PMID: 3033029
  11. The pathophysiology of human mesial temporal lobe epilepsy.
    J Clin Neurophysiol. 1995 Jan;12(1):2-22 PMID: 7896906
  12. Role of the hippocampus in epilepsy.
    Hippocampus. 1994 Jun;4(3):239-42 PMID: 7842043
  13. Repeated electroconvulsive shocks cause transient changes in rat hippocampal somatostatin and neuropeptide Y immunoreactivity and mRNA in situ hybridization signals.
    Exp Brain Res. 1994;98(2):305-13 PMID: 7914171
  14. Short-term synaptic plasticity.
    Annu Rev Neurosci. 1989;12:13-31 PMID: 2648947
  15. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.
    Br J Pharmacol. 1991 Jan;102(1):41-4 PMID: 1646061
  16. Frequency and voltage-dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line, by local anesthetic, antiarrhythmic, and anticonvulsant drugs.
    Mol Pharmacol. 1991 Nov;40(5):756-65 PMID: 1658608
  17. On the sites of presynaptic inhibition by neuropeptide Y in rat hippocampus in vitro.
    Hippocampus. 1993 Jan;3(1):103-11 PMID: 8395947
  18. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y.
    Nature. 1996 May 30;381(6581):415-21 PMID: 8632796
  19. Update on the mechanism of action of antiepileptic drugs.
    Epilepsia. 1996;37 Suppl 6:S4-11 PMID: 8941036
  20. Investigations into neuropeptide Y-mediated presynaptic inhibition in cultured hippocampal neurones of the rat.
    Br J Pharmacol. 1992 Oct;107(2):334-40 PMID: 1358389
  21. Quantitative autoradiographic distribution of [125I]Bolton-Hunter neuropeptide Y receptor binding sites in rat brain. Comparison with [125I]peptide YY receptor sites.
    Neuroscience. 1990;36(1):255-83 PMID: 2170863
  22. Neuronal localisation of neuropeptide Y gene expression in rat brain.
    J Comp Neurol. 1989 Dec 15;290(3):358-68 PMID: 2592617
  23. A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro.
    J Physiol. 1984 Mar;348:239-54 PMID: 6716285
  24. Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons.
    Science. 1978 May 19;200(4343):775-7 PMID: 205953
  25. Somatostatin, neuropeptide Y, GABA and cholinergic enzymes in brain of pentylenetetrazol-kindled rats.
    Neuropeptides. 1989 Oct;14(3):197-207 PMID: 2575717
  26. Kindling induces transient changes in neuronal expression of somatostatin, neuropeptide Y, and calbindin in adult rat hippocampus and fascia dentata.
    Epilepsia. 1994 Nov-Dec;35(6):1299-308 PMID: 7988524
  27. Lamellar organization of hippocampal excitatory pathways.
    Acta Physiol Scand. 1969 May-Jun;76(1):4A-5A PMID: 5823402
  28. Abnormal neuronal excitability in hippocampal slices from kindled rats.
    J Neurophysiol. 1985 Nov;54(5):1295-304 PMID: 3001236
  29. Neuropeptides in perspective: the last ten years.
    Neuron. 1991 Dec;7(6):867-79 PMID: 1684901
  30. Kainic acid seizures in the rat.
    Prog Neurobiol. 1994 Jan;42(1):1-32 PMID: 7480784
  31. Autoradiographic analysis of neuropeptide Y receptor binding sites in the rat hippocampus after kainic acid-induced limbic seizures.
    Neuroscience. 1996 Jan;70(1):47-55 PMID: 8848135
  32. Inhibitory effect of NPY on the picrotoxin-induced activity in the hippocampus: a behavioural and electrophysiological study.
    Neuropeptides. 1996 Feb;30(1):7-12 PMID: 8868293
  33. Functional changes in neuropeptide Y- and somatostatin-containing neurons induced by limbic seizures in the rat.
    Neuroscience. 1992 Oct;50(4):831-46 PMID: 1360155
  34. Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study.
    Brain Res. 1993 Jul 9;616(1-2):263-72 PMID: 8358618
  35. Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat.
    Neurosci Lett. 1990 May 4;112(2-3):143-8 PMID: 2359514
  36. Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology.
    J Neurophysiol. 1997 Jan;77(1):126-36 PMID: 9120553
  37. Altered brain contents of neuropeptides in spontaneously epileptic rats (SER) and tremor rats with absence seizures.
    Life Sci. 1995;57(6):523-31 PMID: 7623620
  38. Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition.
    J Neurosci. 1988 Oct;8(10):3827-37 PMID: 2848110
  39. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro.
    J Physiol. 1982 Jul;328:105-23 PMID: 7131309
  40. Neuropeptide Y distribution in the rat brain.
    Science. 1983 Aug 26;221(4613):877-9 PMID: 6136091
  41. Release of peptide cotransmitters in Aplysia: regulation and functional implications.
    J Neurosci. 1996 Dec 15;16(24):8105-14 PMID: 8987835
  42. Powerful inhibition of kainic acid seizures by neuropeptide Y via Y5-like receptors.
    Nat Med. 1997 Jul;3(7):761-4 PMID: 9212103
  43. The anatomy of neuropeptide-Y-containing neurons in rat brain.
    Neuroscience. 1985 Aug;15(4):1159-81 PMID: 3900805
  44. Enhanced neuropeptide Y release in the hippocampus is associated with chronic seizure susceptibility in kainic acid treated rats.
    Brain Res. 1994 Oct 10;660(1):138-43 PMID: 7827990
  45. Inhibitory effect of neuropeptide y on epileptiform activity in the frontal cortex and hippocampus in vitro.
    Pol J Pharmacol. 1995 Sep-Oct;47(5):461-3 PMID: 8868141
  46. Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes.
    Pharmacol Rev. 1995 Jun;47(2):181-234 PMID: 7568326
  47. Presynaptic action of neuropeptide Y in area CA1 of the rat hippocampal slice.
    J Physiol. 1987 Feb;383:285-99 PMID: 2821236
  48. Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons.
    Neurosci Lett. 1990 Aug 14;116(1-2):233-8 PMID: 2175404
  49. Neuropeptide Y: complete amino acid sequence of the brain peptide.
    Proc Natl Acad Sci U S A. 1982 Sep;79(18):5485-9 PMID: 6957876
  50. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus.
    Nature. 1996 Jun 20;381(6584):706-9 PMID: 8649517
  51. Autoradiographic distribution of [125I]Leu31,Pro34]PYY and [125I]PYY3-36 binding sites in the rat brain evaluated with two newly developed Y1 and Y2 receptor radioligands.
    Synapse. 1996 Feb;22(2):139-58 PMID: 8787130
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1997-12-01
Pages
8927-36
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6573608
Subset
IM
Grants
NINDS NIH HHS · NS-07114 · United States
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2