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Altered Hippocampal Expression of Neuropeptides in Seizure‐prone GALR1 Knockout Mice
Author(s) -
Fetissov Sergueï O.,
Jacoby Arie S.,
Brumovsky Pablo R.,
Shine John,
Iismaa Tiina P.,
Hökfelt Tomas
Publication year - 2003
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2003.51402.x
Subject(s) - galanin , neuropeptide , neuropeptide y receptor , medicine , endocrinology , hippocampal formation , dentate gyrus , dynorphin , in situ hybridization , granule cell , knockout mouse , chemistry , downregulation and upregulation , enkephalin , biology , messenger rna , receptor , opioid peptide , biochemistry , opioid , gene
Summary: Purpose: 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.