title: Antidepressant-like effects exerted by the intranasal administration of a glucagon-like peptide-2 derivative containing cell-penetrating peptides and a penetration-accelerating sequence in mice.
abstract: The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine-resistant depression-model mice. In order to utilize GLP-2 as a clinical treatment tool for depression, we herein focused on the intranasal delivery that is non-invasive approach, because the i.c.v. administration is invasive and impractical. In the present study, we prepared a GLP-2 derivative containing cell penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS-CPPs-GLP-2) for the intranasal (i.n.) administration. PAS-CPPs-GLP-2 (i.n.) exhibited antidepressant-like effects in the forced-swim test (FST) and tail suspension test (TST) in naïve mice as well as adrenocorticotropic hormone (ACTH) treated-mice. However, PAS-CPPs-GLP-2 (i.v.) and the GLP-2 derivative containing CPPs without a PAS (CPPs-GLP-2) (i.n.) did not affect the immobility time in the mouse FST. Moreover, fluorescein isothiocyanate (FITC)-labeled PAS-CPPs-GLP-2 (i.n.), but not FITC-labeled CPPs-GLP-2 (i.n.) was distributed through the mouse brain after the FST session. These results suggest that PAS-CPPs-GLP-2 is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of major depression.
authors.affiliation: Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Translational Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Sasaki-Hamada
authors.affiliation: Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Laboratory of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Sanai
authors.affiliation: Laboratory of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Laboratory of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Horiguchi
authors.affiliation: Laboratory of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Chikamasa
authors.initials: C
authors.lastname: Yamashita
authors.affiliation: Laboratory of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Translational Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. Electronic address: okaji@rs.noda.tus.ac.jp.
authors.forename: Jun-Ichiro
authors.initials: JI
authors.lastname: Oka
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000737:chemistry; D001921:Brain / Q000187:drug effects / Q000473:pathology; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D005934:Glucagon / Q000378:metabolism; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice
chemical_list: D000928:Antidepressive Agents; D057846:Cell-Penetrating Peptides; D053767:Glucagon-Like Peptide 2; D005934:Glucagon
keywords: Antidepressant; Brain drug delivery and targeting; Glucagon-like peptide-2; Intranasal administration