title: Altered hippocampal expression of neuropeptides in seizure-prone GALR1 knockout mice.
abstract: OBJECTIVE
  Mice carrying a deletion of the GALR1 galanin receptor have recently showed spontaneous seizure phenotype with 25% penetrance. To better understand the role of neuropeptides, which are known to undergo complex plasticity changes with development of epileptic seizures, we characterized their expression in the hippocampal formation in GALR1- knockout (-KO) mice with or without seizures and in wild-type (WT) mice.
  
  
  METHODS
  Immunohistochemistry and in situ hybridization were used to study expression of galanin, neuropeptide Y (NPY), substance P, enkephalin, dynorphin, and cholecystokinin (CCK).
  
  
  RESULTS
  In GALR1-KO mice that had been displaying seizures, a strong upregulation of galanin immunoreactivity (ir) and messenger RNA (mRNA) was found in the polymorph layer of the dentate gyrus; galanin-ir also appeared in a dense fiber network in the supragranular layer. A strong upregulation of enkephalin was found in the granule cells/mossy fibers, whereas dynorphin mRNA levels were modestly decreased. NPY was strongly expressed in the granule cells/mossy fibers, and an increase of NPY mRNA levels in the polymorph cells was paralleled by an increase of NPY-ir in the molecular layer. An upregulation of substance P-ir was confined to the fibers in the granule and molecular layers, whereas substance P mRNA was increased in the cells of the polymorph layer. Both CCK-ir and mRNA were strongly downregulated in the granule cell/mossy fiber system, but CCK-ir appeared increased in the supragranular and molecular layers. No changes in neuropeptide-ir were found in GALR1-KO mice not displaying seizures.
  
  
  CONCLUSIONS
  Complex changes in neuropeptide expression in some principal hippocampal neurons and interneurons appear as a characteristic feature of the spontaneous-seizure phenotype in GALR1-KO mice. However, to what extent causal relations exist between this "epilepsia peptidergic profile" and development of seizures requires further clarification.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Serguei.Fetissov@neuro.ki.se
authors.forename: Sergueï O
authors.initials: SO
authors.lastname: Fetissov
authors.forename: Arie S
authors.initials: AS
authors.lastname: Jacoby
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Brumovsky
authors.forename: John
authors.initials: J
authors.lastname: Shine
authors.forename: Tiina P
authors.initials: TP
authors.lastname: Iismaa
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000473:pathology; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D019599:Mossy Fibers, Hippocampal / Q000473:pathology; D016254:Mutagenesis, Insertional; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics*; D010641:Phenotype; D017966:Pyramidal Cells / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics*
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide