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 -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-1 [IL-1], and H2O2). In the Y-maze test, LPS (10 g/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 g/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-1 (0.57 nM) or H2O2 (50 M) 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. (c) 2014 Wiley Periodicals, Inc.