Effect of chronic intracerebroventricular insulin administration in rats on the peripheral glucose metabolism and synaptic plasticity of CA1 hippocampal neurons
Effect of chronic intracerebroventricular insulin administration in rats on the peripheral glucose metabolism and synaptic plasticity of CA1 hippocampal neurons
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DOI：
10.1016/j.brainres.2011.11.057
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发表时间：
2012-01-30
期刊：
影响因子：
2.9
通讯作者：
Biessels, Geert Jan
中科院分区：
文献类型：
--
作者：
Kamal, Amer;Ramakers, Geert M. J.;Biessels, Geert Jan
在本研究中，我们观察了脑室持续注射胰岛素对大鼠海马区突触可塑性的影响。用渗透压微泵给雄性Wistar大鼠(n=12)侧脑室注入胰岛素3个月。对照组(n=12)接受假手术。胰岛素注射最初导致食物摄入量和体重增加减少，但这些差异在12周后减弱。胰岛素输注不影响空腹或非空腹血糖水平。海马场突触电位记录显示，长时程增强的表达存在缺陷。锐尖电极电流钳记录显示，CA1区锥体细胞在长时间注入去极化电流后产生动作电位，且动作电位呈进行性加宽。胰岛素灌流动物的动作电位展宽明显长于对照组。以65 mV手动“钳制”细胞，注入电流诱发4个AP后，测量慢后超极化(SAHP)的幅度。SAHP波幅明显长于对照组。我们的结论是，在对全身血糖水平没有明显影响的情况下，局部胰岛素脑内注射对突触可塑性有显著影响。这些结果表明，胰岛素水平的长期升高可能会直接对大脑产生不利影响。(C)2011爱思唯尔B.V.保留所有权利。
In this study we examined the effects of sustained intracerebroventricular insulin infusion on hippocampal synaptic plasticity in rats. Insulin was infused intracerebroventricularly in male Wistar rats (n=12) for 3 months using osmotic minipumps. A control group (n=12) received a sham operation. Insulin infusion led to an initial reduction in food intake and body weight gain, but these differences attenuated over 12 weeks. Insulin infusion did not affect fasting or non-fasting blood glucose levels. Field synaptic potentials recording from the hippocampus demonstrated a defect in the expression of long-term potentiation. Sharp electrode current-clamp recording showed that CA1 pyramidal cells fire action potentials in response to prolonged depolarizing current injection and those action potentials showed progressive broadening. The action potential broadening in the insulin-perfused animals were significantly longer than the control. The amplitude of slow after hyperpolarization (sAHP) was measured after manually "clamping" the cells at 65 mV and injecting currents to evoke a train of four APs. The sAHP amplitude was significantly longer than in the control animals. We conclude that local insulin infusion into the brain of rats had significant effects on synaptic plasticity in the absence of marked effects on systemic glucose levels. These results indicate that long-term elevation of insulin levels can have adverse effects directly on the brain. (C) 2011 Elsevier B.V. All rights reserved.