Glucagon-like peptide-2-induced memory improvement and anxiolytic effects in mice. (February 2015)

• Record Type: Journal Article
• Authors: Iwai, Takashi; Jin, Kazushi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Nakamura, Minami; Saitoh, Akiyoshi; Sugiyama, Azusa; Ikeda, Masaatsu; Tanabe, Mitsuo; Oka, Jun-Ichiro
• Is Part Of: Neuropeptides. Volume 49(2015)
• Page Start: 7
• Page End: 14
• Publication Date: 2015-02
• Subjects: ACTH adrenocorticotropic hormone -- DRN dorsal raphe nucleus -- 5-HT serotonin -- 5-HIAA 5-hydroxyindoleacetic acid -- HPA hypothalamic-adrenal axis -- GLP-2 glucagon-like peptide-2 -- LPS lipopolysaccharide -- PBS phosphate-buffered saline -- PCPA p-chlorophenylalanine -- TPH tryptophan hydroxylase; Glucagon-like peptide-2 -- Y-maze -- Elevated plus-maze -- Antidepressant -- Anxiety -- Major depression -- Serotonin -- ACTH; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2014.11.001
• Languages: English
• ISSNs: 0143-4179

Abstract

Highlights: Pretreatment of GLP-2 prevented the development of memory impairment induced by LPS. >GLP-2 improved the LPS-induced memory impairment. >GLP-2 showed weak anxiolytic-like effects in ACTH-treated, but not saline-treated mice. >GLP-2 increased 5-HT, but not 5-HIAA levels in amygdala. GLP-2 influenced memory functions and had anxiolytic effects via the 5-HT system. Abstract: We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) on memory impairment in lipopolysaccharide (LPS)-treated mice, and anxiety-like behavior in adrenocorticotropic hormone (ACTH)-treated mice. In the Y-maze test, LPS (10 µg/mouse, i.c.v.) significantly decreased spontaneous alternation, which was prevented by pretreatment with GLP-2 (0.01–0.3 µg/mouse, i.c.v.). The GLP-2 treatment just before the Y-maze test also improved LPS-induced memory impairment. Continuous treatment with GLP-2 (3 µg/mouse, i.c.v.) had no effect on the open-field test in saline-treated or ACTH-treated mice. Chronic ACTH treatment did not cause anxiogenic effects in the elevated plus-maze test. GLP-2 showed weak anxiolytic-like effects in the elevated plus-maze test in ACTH-treated, but not saline-treated mice. Moreover, GLP-2 increased 5-HT, but not 5-HIAA and tryptophan hydroxylase 2 levels in the amygdala of ACTH-treated mice. Pharmacological depletion of 5-HT prevented the anxiolytic effects of GLP-2. These results suggest that GLP-2 protected and improved memory function in LPS-treated mice, and also had anxiolytic effects due to changes in the 5-HT system.