Exendin (5-39), an antagonist of GLP-1 receptor, modulates synaptic transmission via glutamate uptake in the dentate gyrus.
Brain Res, 2013/4/10;1505:1-10.
Kobayashi K[1], Iwai T, Sasaki-Hamada S, Kamanaka G, Oka J
Affiliations
PMID: 23318256
Impact factor: 3.61
Abstract
Extracellular concentrations of glutamate are mainly controlled by an astrocytic glutamate transporter, GLT-1. We previously reported that exendin (5-39) (Ex), an antagonist of the GLP-1 receptor, improved memory impairment in β-amyloid protein-treated rats. In this study, we investigated effects of Ex on synaptic transmission through astrocytic GLT-1 in the hippocampus. Continuous intracerebroventricular (i.c.v.) administration of Ex for 1-week increased GLT-1 protein levels in the hippocampus of 4-week-old male Wistar rats. For electrophysiological studies, hippocampal slices were prepared from these Ex-treated rats or vehicle-treated rats. Ex decreased fEPSP decay time, and increased the input-output relation and decreased the paired-pulse ratio in the dentate gyrus (DG). Furthermore, Ex inhibited long-term depression but not long-term potentiation in the DG. These effects were prevented by DHK, a specific GLT-1 inhibitor. In addition, glutamate uptake was significantly increased by Ex-treatment in cultured astrocytes. These results suggest that Ex modulates synaptic transmission and plasticity through astrocytic glutamate uptake in the DG.
MeSH terms
Analysis of Variance; Animals; Biophysics; Cells, Cultured; Dentate Gyrus; Electric Stimulation; Embryo, Mammalian; Excitatory Amino Acid Agonists; Female; Gene Expression Regulation; Glucagon-Like Peptide-1 Receptor; Glutamic Acid; In Vitro Techniques; Kainic Acid; Long-Term Potentiation; Long-Term Synaptic Depression; Neuroglia; Patch-Clamp Techniques; Peptide Fragments; Pregnancy; RNA, Messenger; Rats; Rats, Wistar; Receptors, Glucagon; Synaptic Transmission
More resources
EndNote: Download