Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.
Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.
复制标题
胰岛素信号障碍，脂联素和血脂异常在小鼠外周和中枢神经病中的作用。
DOI：
10.1242/dmm.015750
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发表时间：
2014-06
影响因子：
4.3
通讯作者：
Jolivalt CG
中科院分区：
文献类型：
--
作者：
Anderson NJ;King MR;Delbruck L;Jolivalt CG
受糖尿病影响的组织或器官之一是神经系统，主要是外周系统（外周多发性神经病和/或疼痛性周围神经病），但也包括学习、记忆和心理灵活性受损的中枢系统。本研究的目的是检验由高脂饮食（HFD）引起的糖尿病前期或糖尿病状态可损害外周和中枢神经系统的假设。给C57 BL 6和Swiss韦伯斯特小鼠组喂食含有60%脂肪的饮食8个月，并与对照组和链脲佐菌素（STZ）诱导的糖尿病组进行比较，后者喂食含有10%脂肪的标准饮食。在研究期间的不同时间测量外周神经功能（传导速度、热敏感性）和中枢神经系统功能（学习能力、记忆力）。HFD的两种小鼠品系均出现葡萄糖耐量受损，表明胰岛素抵抗，但只有C57 BL 6小鼠显示统计学显著的高血糖症。STZ糖尿病C57 BL 6小鼠在糖尿病8周后在巴恩斯迷宫中出现学习缺陷，而喂食HFD的C57 BL 6和Swiss韦伯斯特小鼠在该时间点均未显示缺陷迹象。在HFD治疗6个月后，瑞士韦伯斯特小鼠在巴恩斯迷宫测试中出现学习和记忆缺陷，而它们的外周神经系统保持正常。相反，喂食HFD的C57 BL 6小鼠出现外周神经功能障碍，如神经传导减慢和热痛觉过敏所示，但表现出正常的学习和记忆功能。我们的数据表明，STZ诱导的糖尿病或HFD可以损害外周和中枢神经系统，但学习缺陷的发展更迅速，在胰岛素缺乏比胰岛素抵抗的条件下，只有在瑞士韦伯斯特小鼠。除了胰岛素受损，血脂异常或脂联素血症可能决定神经病变的表型。
One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype.
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