RGD Reference Report - Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. - Rat Genome Database

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Glucagon-like peptide-1 receptor is involved in learning and neuroprotection.

Authors: During, MJ  Cao, L  Zuzga, DS  Francis, JS  Fitzsimons, HL  Jiao, X  Bland, RJ  Klugmann, M  Banks, WA  Drucker, DJ  Haile, CN 
Citation: During MJ, etal., Nat Med. 2003 Sep;9(9):1173-9. Epub 2003 Aug 17.
RGD ID: 1598440
Pubmed: PMID:12925848   (View Abstract at PubMed)
DOI: DOI:10.1038/nm919   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
status epilepticus  ISOGlp1r (Mus musculus)1598440; 1598440 RGD 
status epilepticus  IMP 1598440 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
associative learning  IDA 1598440 RGD 
learning or memory involved_inIMP 1598440PMID:12925848UniProt 
memory  IDA 1598440 RGD 
negative regulation of neuron apoptotic process  IDA 1598440 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Glp1r  (glucagon-like peptide 1 receptor)

Genes (Mus musculus)
Glp1r  (glucagon-like peptide 1 receptor)

Genes (Homo sapiens)
GLP1R  (glucagon like peptide 1 receptor)


Additional Information