Impact of morphine on the expression of insulin receptor and protein levels of insulin/IGFs in rat neural stem cells. (1st November 2017)

• Record Type: Journal Article
• Authors: Salarinasab, Sadegh; Nourazarian, AliReza; Nikanfar, Masoud; Abdyazdani, Nima; Kazemi, Masoumeh; Feizy, Navid; Rahbarghazi, Reza
• Is Part Of: Neuroscience letters. Volume 660(2017)
• Page Start: 147
• Page End: 154
• Publication Date: 2017-11-01
• Subjects: Rat neural stem cells -- Morphine -- Insulin -- Insulin receptor -- Insulin- like growth factor1 and 2; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.09.035
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Morphine increase cell apoptosis and decrease rat neural stem cell growth. Morphine decrease of insulin, insulin-like growth factors biosynthesis in rat neural stem. Morphine down-regulate of insulin receptor in rat neural stem. Abstract: Alzheimer's disease is correlated with neuronal degeneration and loss of neuronal precursors in different parts of the brain. It has been found disturbance in the homeostasis neural stem cells (NSCs) can cause neurodegeneration. Morphine, an analgesic agent, can disrupt the dynamic and normal state of NSCs. However, more investigations are required to clearly address underlying mechanisms. The current experiment aimed to investigate the effects of morphine on the cell distribution of insulin factor and receptor and insulin-like growth factors (IGF1, IGF2) in NSCs. NSCs were isolated from rats and stemness feature confirmed by antibodies against nestin and Sox2. The cells were exposed to 100 μM morphine, 50 μM naloxone and combination of these two drugs for 72 h. The neural cell growth, changes in levels of insulin and insulin-like growth factors secreted by NSCs as well as the insulin-receptor-gene expression were assessed by flow cytometry, ELlSA, and real-time PCR, respectively. Cell cycle assay revealed the exposure of cells to morphine for 72 h increased cell apoptosis and decreased neural stem cell growth. The biosynthesis of insulin, insulin-like growth factors, and insulin receptor were reduced (p < 0.05) after NSCs exposure to morphine at the concentration of 100 μM for 24, 48 and 72 h. Naloxone is a competitive antagonist which binds MOR where morphine (and endogenous opioids) bind, and reversed the detrimental effects of morphine. It can be concluded that morphine initiated irregularity in NSCs kinetics and activity by reducing the secretion of insulin and insulin-like growth factors and down-regulation of insulin receptor.