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Glucagon‐like peptide‐1 protects synaptic and learning functions from neuroinflammation in rodents
Author(s) -
Iwai Takashi,
Sawabe Toshihiro,
Tanimitsu Kahori,
Suzuki Manabu,
SasakiHamada Sachie,
Oka JunIchiro
Publication year - 2014
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23335
Subject(s) - neuroinflammation , spontaneous alternation , proglucagon , long term potentiation , ltp induction , hippocampus , incretin , hippocampal formation , nmda receptor , inflammation , glucagon like peptide 1 , endocrinology , medicine , chemistry , pharmacology , receptor , diabetes mellitus , type 2 diabetes
Glucagon‐like peptide‐1 (GLP‐1) is derived from the processing of proglucagon in intestinal L‐cells and releases insulin from pancreatic β‐cells as an incretin. The GLP‐1 receptor has been proposed as a possible therapeutic target for the treatment of Alzheimer's disease, in which neuroinflammation is critical in the pathogenesis. The present study investigates whether GLP‐1 (7–36) amide, an active fragment of GLP‐1, protected against synaptic impairments induced by inflammation‐related injurious agents (lipopolysaccharide [LPS], interleukin‐1β [IL‐1β], and H 2 O 2 ). In the Y‐maze test, LPS (10 μg/mouse, i.c.v) significantly decreased the percentage alternation. Pretreatment with GLP‐1 (7–36) amide (0.09–0.9 nmol/mouse, i.c.v.) prevented an impairment in spontaneous alternation performance. Pretreatment with LPS (10 μg/ml, 2 hr) impaired LTP induction but not paired‐pulse facilitation in the CA1 region of rat hippocampal slices. This impairment was prevented by cotreatment with GLP‐1 (7–36) amide (50 nM). IL‐1β (0.57 nM) or H 2 O 2 (50 μM) also impaired LTP induction. This impairment was prevented by GLP‐1 (7–36) amide (50 nM). These results suggest that GLP‐1 (7–36) amide improves the synaptic impairments induced by inflammation‐related injurious agents in the CA1 region of the hippocampus. © 2014 Wiley Periodicals, Inc.