Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment

Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment
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DOI:
10.1016/s0006-8993(98)00510-1
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发表时间:
1998-07-27
期刊:
影响因子:
2.9
通讯作者:
Gispen, WH
Gispen, WH
中科院分区:
医学3区
文献类型:
--
作者:
Biessels, GJ;Kamal, A;Gispen, WH

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链脲佐菌素糖尿病大鼠表达水迷宫学习和海马突触可塑性缺陷。本研究探讨了这些缺陷是否可以预防和/或逆转胰岛素治疗。此外,进一步表征了糖尿病大鼠的水迷宫学习缺陷。在预防实验中,在糖尿病发作时开始胰岛素治疗,在逆转实验中,在糖尿病诱导后10周开始胰岛素治疗。治疗10周后,在空间版本的Morris水迷宫中测试胰岛素治疗的糖尿病大鼠、未治疗的糖尿病大鼠和非糖尿病对照。接下来,在体外测量海马长时程增强(LTP)。为了进一步表征糖尿病对水迷宫学习的影响,在暴露于空间版本之前,在迷宫的非空间版本中对单独的一组大鼠进行预训练。糖尿病大鼠水迷宫学习和海马LTP均受损。在糖尿病发作时开始的胰岛素治疗可预防这些损害。在逆转实验中,胰岛素治疗未能逆转迷宫学习中的既定缺陷,仅部分恢复LTP。非空间预训练消除了糖尿病大鼠在空间迷宫中的表现缺陷。结论:胰岛素治疗可以预防但不能逆转链脲佐菌素糖尿病大鼠水迷宫学习和LTP的缺陷。预训练实验表明,糖尿病大鼠在水迷宫的空间版本中的性能缺陷与学习迷宫程序的困难有关,而不是空间学习障碍。(C)1998 Elsevier Science B. V.保留所有权利。
Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characterized. Insulin treatment was commenced at the onset of diabetes in a prevention experiment, and 10 weeks after diabetes induction in a reversal experiment. After 10 weeks of treatment, insulin-treated diabetic rats, untreated diabetic rats and non-diabetic controls were tested in a spatial version of the Morris water maze. Next, hippocampal long-term potentiation (LTP) was measured in vitro. To further characterize the effects of diabetes on water maze learning, a separate group of rats was pre-trained in a non-spatial version of the maze, prior to exposure to the spatial version. Both water maze learning and hippocampal LTP were impaired in diabetic rats. Insulin treatment commenced at the onset of diabetes prevented these impairments. In the reversal experiment, insulin treatment failed to reverse established deficits in maze learning and restored LTP only partially. Non-spatial pre-training abolished the performance deficit of diabetic rats in the spatial version of the maze. It is concluded that insulin treatment may prevent but not reverse deficits in water maze learning and LTP in streptozotocin-diabetic rats. The pre-training experiment suggests that the performance deficit of diabetic rats in the spatial version of the water maze is related to difficulties in learning the procedures of the maze rather than to impairments of spatial learning. (C) 1998 Elsevier Science B.V. All rights reserved.