title: Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice.
abstract: Exenatide is a potent and selective agonist for the GLP-1 (glucagon-like peptide-1) receptor. Recent studies are focused on the effects of GLP-1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 μg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real-time polymerase chain reaction (RT-PCR). This study revealed that in the mEPM and PA tests, type-2 diabetes-induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP-1 receptor agonist exenatide. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA-induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder.
authors.affiliation: Department of Medical Genetics, Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Esen
authors.initials: E
authors.lastname: Gumuslu
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Oguz
authors.initials: O
authors.lastname: Mutlu
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Ipek K
authors.initials: IK
authors.lastname: Celikyurt
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Guner
authors.initials: G
authors.lastname: Ulak
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Furuzan
authors.initials: F
authors.lastname: Akar
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Faruk
authors.initials: F
authors.lastname: Erden
authors.affiliation: Department of Medical Genetics, Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Ertan
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000077270:Exenatide; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: BDNF; CREB; exenatide; memory; type-2 diabetes