title: Immunohistochemical determination of the site of antidepressant-like effects of glucagon-like peptide-2 in ACTH-treated mice.
abstract: The intracerebroventicular administration (i.c.v.) of glucagon-like peptide-2 (GLP-2) had antidepressant-like effects on saline-treated mice in the forced-swim test. The GLP-2 treatment (3 μg, i.c.v.) for 6 days, but not that of imipramine had antidepressant-like effects on adrenocorticotropic hormone (ACTH)-treated mice. The immunohistochemical detection of the c-fos protein (Fos) revealed that the administration of GLP-2 induced Fos-immunoreactivity (Fos-IR) in the dorsomedial hypothalamic nucleus in saline-treated and ACTH-treated mice, and also in the hippocampal dentate gyrus in ACTH-treated mice, but not in saline-treated mice. In contrast, Fos-IR in the paraventricular nucleus of the hypothalamus decreased after the administration of GLP-2 to ACTH-treated mice. In ACTH-treated mice, the chronic administration of GLP-2 affected hippocampal neurogenesis, in addition to Fos-IR in hypothalamic GABAergic neurons and corticotrophin-releasing factor-containing neurons. These results suggest that GLP-2 acts on specific brain regions to regulate stress conditions, and induces antidepressant-like effects under imipramine-resistant conditions, which may be associated with the modulation of the hypothalamic-pituitary-adrenal-axis.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sasaki-Hamada
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuri
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hoshi
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: okaji@rs.noda.tus.ac.jp.
authors.forename: J-I
authors.initials: JI
authors.lastname: Oka
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D053767:Glucagon-Like Peptide 2; D016760:Proto-Oncogene Proteins c-fos; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone
keywords: CRF; adrenocorticotropic hormone; antidepressant; c-fos protein; glucagon-like peptide-2; neurogenesis