Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice


Gumuslu E., Mutlu O., Celikyurt I. K., Ulak G., Akar F., Erden F., ...Daha Fazla

FUNDAMENTAL & CLINICAL PHARMACOLOGY, cilt.30, ss.376-384, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1111/fcp.12192
  • Dergi Adı: FUNDAMENTAL & CLINICAL PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.376-384
  • Anahtar Kelimeler: BDNF, CREB, exenatide, memory, type-2 diabetes, GLUCAGON-LIKE PEPTIDE-1, HIPPOCAMPAL SYNAPTIC PLASTICITY, LONG-TERM POTENTIATION, GLUCOSE-METABOLISM, INSULIN-RESISTANCE, RECEPTOR, BRAIN, MEMORY, GLP-1, BETA
  • Kocaeli Üniversitesi Adresli: Evet

Özet

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 g/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.