Glucagon‐like peptide‐1 protects synaptic and learning functions from neuroinflammation in rodents

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 H₂O₂). 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 H₂O₂ (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.