Gumuslu Esen, Mutlu Oguz, Celikyurt Ipek K, Ulak Guner, Akar Furuzan, Erden Faruk, Ertan Merve
Department of Medical Genetics, Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
Department of Medical Pharmacology, Psychopharmacology Lab., Medical Faculty, Kocaeli University, Kocaeli, 41380, Turkey.
Fundam Clin Pharmacol. 2016 Aug;30(4):376-84. doi: 10.1111/fcp.12192. Epub 2016 Mar 21.
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.
艾塞那肽是一种强效且具有选择性的胰高血糖素样肽-1（GLP-1）受体激动剂。近期研究聚焦于GLP-1类似物对海马神经发生、认知、学习和记忆功能的影响。本研究旨在通过改良高架十字迷宫（mEPM）试验评估慢性艾塞那肽治疗（0.1μg/kg，皮下注射，每日两次，共2周）对链脲佐菌素/烟酰胺（STZ-NA）诱导的糖尿病小鼠空间记忆功能的影响，并通过被动回避（PA）试验评估其对情绪记忆功能的影响。由于参与神经突重塑的基因是主要调控靶点之一，还使用定量实时聚合酶链反应（RT-PCR）测定了糖尿病及艾塞那肽慢性给药对小鼠海马中脑源性神经营养因子（BDNF）和环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）信使核糖核酸（mRNA）水平的影响。本研究表明，在mEPM和PA试验中，2型糖尿病诱导的小鼠表现出显著的学习和记忆障碍，而GLP-1受体激动剂艾塞那肽可改善这些障碍。定量RT-PCR显示，糖尿病小鼠中CREB和BDNF基因表达水平下调，而艾塞那肽治疗可加剧这些改变。由于艾塞那肽可改善STZ/NA诱导的糖尿病小鼠的认知能力，并激活与学习经历相关的记忆存储分子机制，它可能是缓解情绪和认知障碍的候选药物。
