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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats
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Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats

机译：吡格列酮和艾塞那肽增强胰岛素抵抗大鼠的认知并下调海马β淀粉样蛋白寡聚体和小胶质细胞的表达

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摘要

Insulin resistance is known to be a risk factor for cognitive impairment, most likely linked to insulin signaling, microglia overactivation, and beta amyloid (A beta) deposition in the brain. Exenatide, a long lasting glucagon-like peptide-1 (GLP-1) analogue, enhances insulin signaling and shows neuroprotective properties. Pioglitazone, a peroxisome proliferated-activated receptor-gamma (PPAR-gamma) agonist, was previously reported to enhance cognition through its effect on A beta accumulation and clearance. In the present study, insulin resistance was induced in male rats by drinking fructose for 12 weeks. The effect of monotherapy with pioglitazone (10 mg.kg(-1)) and exenatide or their combination on memory dysfunction was determined and some of the probable underlying mechanisms were studied. The current results confirmed that (1) feeding male rats with fructose syrup for 12 weeks resulted in a decline of learning and memory registered in eight-arm radial maze test; (2) treatment with pioglitazone or exenatide enhanced cognition, reduced hippocampal neurodegeneration, and reduced hippocampal microglia expression and beta amyloid oligomer deposition in a manner that is equal to monotherapies. These results may give promise for the use of pioglitazone or exenatide for ameliorating the learning and memory deficits associated with insulin resistance in clinical setting.
机译：已知胰岛素抵抗是认知障碍的危险因素，最有可能与胰岛素信号传导，小胶质细胞过度活化和大脑中的β淀粉样蛋白（A beta）沉积有关。艾塞那肽是一种长效胰高血糖素样肽1（GLP-1）类似物，可增强胰岛素信号传导并显示神经保护特性。吡格列酮是一种过氧化物酶体增殖激活受体-γ（PPAR-γ）激动剂，以前有报道通过其对Aβ积累和清除的作用来增强认知能力。在本研究中，通过饮用果糖12周可诱导雄性大鼠胰岛素抵抗。确定了吡格列酮（10 mg.kg（-1））和艾塞那肽或其组合对记忆功能障碍的单药治疗效果，并研究了一些可能的潜在机制。目前的结果证实：（1）用果糖糖浆喂养雄性大鼠12周导致八臂放射状迷宫测试中记录的学习和记忆下降; （2）吡格列酮或艾塞那肽治疗的疗效与单一疗法相同，可增强认知能力，减少海马神经变性，减少海马小胶质细胞表达和β淀粉样蛋白低聚物沉积。这些结果为使用吡格列酮或艾塞那肽改善临床环境中与胰岛素抵抗相关的学习和记忆障碍提供了希望。

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