Endogenous GLP-1 is involved in beta-amyloid protein-induced memory impairment and hippocampal neuronal death in rats.
We examined the effects of continuous infusion of exendin (5-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptors, into the rat brain using a mini-osmotic pump on beta-amyloid protein-induced amnesia and apoptosis. Co-infusion of exendin (5-39) with beta-amyloid protein (1-40) prevented the memory impairment and DNA fragmentation in the hippocampal CA1 region observed with infusion of beta-amyloid protein alone. These results indicated a functional role of endogenous GLP-1 in beta-amyloid protein-induced neurotoxicity.
Oka
J
J
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Tenpaku-ku, Nagoya 468-8503, Japan. okaji@meijo-u.ac.jp
Suzuki
E
E
Kondo
Y
Y
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D004338:Drug Combinations; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control / Q000523:psychology; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors
D016229:Amyloid beta-Peptides; D004338:Drug Combinations; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; C417195:exendin (5-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon