PMID:12925848

Citation	During, MJ, Cao, L, Zuzga, DS, Francis, JS, Fitzsimons, HL, Jiao, X, Bland, RJ, Klugmann, M, Banks, WA, Drucker, DJ and Haile, CN (2003) Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat. Med. 9:1173-9
Abstract	Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and [Ser(2)]exendin(1-9) (HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. [Ser(2)]exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of [Ser(2)]exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents.
Links	PubMed Online version:10.1038/nm919
Keywords	Administration, Intranasal; Amino Acid Sequence; Animals; Apoptosis/drug effects; Behavior, Animal/drug effects; Cognition/drug effects; Gene Expression; Gene Transfer Techniques; Glucagon/administration & dosage; Glucagon/pharmacology; Glucagon-Like Peptide 1; Hippocampus/cytology; Hippocampus/drug effects; Hippocampus/physiology; Kainic Acid/adverse effects; Learning/drug effects; Learning/physiology; Male; Mice; Mice, Knockout; Molecular Sequence Data; Neurons/drug effects; Neurons/pathology; Neuroprotective Agents/pharmacology; Peptide Fragments/administration & dosage; Peptide Fragments/pharmacology; Protein Precursors/administration & dosage; Protein Precursors/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Glucagon/drug effects; Receptors, Glucagon/genetics; Receptors, Glucagon/metabolism; Seizures/chemically induced; Seizures/genetics; Sequence Homology, Amino Acid; Signal Transduction
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.