The glucagon-like peptide 1 receptor agonist exendin-4 improves reference memory performance and decreases immobility in the forced swim test.
We have earlier shown that the glucagon-like peptide 1 receptor agonist exendin-4 stimulates neurogenesis in the subventricular zone and excerts anti-parkinsonian behavior. The aim of this study was to assess the effects of exendin-4 treatment on hippocampus-associated cognitive and mood-related behavior in adult rodents. To investigate potential effects of exendin-4 on hippocampal function, radial maze and forced swim test were employed. The time necessary to solve a radial maze task and the duration of immobility in the forced swim test were significantly reduced compared to respective vehicle groups if the animals had received exendin-4 during 1-2weeks before testing. In contrast to the positive control imipramine, single administration of exendin-4 1h before the challenge in the forced swim test had no effect. Immunohistochemical analysis showed that the incorporation of bromodeoxyuridine, a marker for DNA synthesis, as well as doublecortin expression was increased in the hippocampal dentate gyrus following chronic treatment with exendin-4 compared to vehicle-treated controls. The neurogenic effect of exendin-4 on hippocampus was confirmed by quantitative PCR showing an upregulation of mRNA expression for Ki-67, doublecortin and Mash-1. Since exendin-4 significantly improves hippocampus-associated behavior in adult rodents, it may be a candidate for alleviation of mood and cognitive disorders.
Isacson
Ruben
R
NeuroNova AB, Fiskartorpsvägen 15 A-D, 114 33 Stockholm, Sweden.
Nielsen
Elisabet
E
Dannaeus
Karin
K
Bertilsson
Göran
G
Patrone
Cesare
C
Zachrisson
Olof
O
Wikström
Lilian
L
D000339:Affect / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000089662:Doublecortin Protein; D004357:Drug Synergism; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists*; D013550:Swimming; D014688:Venoms / Q000494:pharmacology*
D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide; D001973:Bromodeoxyuridine