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 H2 O2). 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 H2 O2 (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.
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Takashi
T
Iwai
Toshihiro
T
Sawabe
Kahori
K
Tanimitsu
Manabu
M
Suzuki
Sachie
S
Sasaki-Hamada
Jun-Ichiro
J
Oka
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology* / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology; D006861:Hydrogen Peroxide / Q000009:adverse effects; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects*
D008070:Lipopolysaccharides; D052216:Glucagon-Like Peptide 1; D006861:Hydrogen Peroxide
GLP-1; LTP; hydrogen peroxide; inflammation; interleukin-1