Biessels G J, Kamal A, Urban I J, Spruijt B M, Erkelens D W, Gispen W H
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, PO Box 80040, 3508 TA, Utrecht, Netherlands.
Brain Res. 1998 Jul 27;800(1):125-35. doi: 10.1016/s0006-8993(98)00510-1.
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.
链脲佐菌素诱导的糖尿病大鼠在水迷宫学习和海马突触可塑性方面表现出缺陷。本研究检测了胰岛素治疗是否可以预防和/或逆转这些缺陷。此外，还进一步对糖尿病大鼠的水迷宫学习缺陷进行了特征描述。在预防实验中，胰岛素治疗在糖尿病发病时开始；在逆转实验中，胰岛素治疗在糖尿病诱导10周后开始。治疗10周后，对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组进行Morris水迷宫空间版本测试。接下来，在体外测量海马长时程增强（LTP）。为了进一步描述糖尿病对水迷宫学习的影响，在另一组大鼠接触空间版本迷宫之前，先在非空间版本迷宫中对其进行预训练。糖尿病大鼠的水迷宫学习和海马LTP均受损。糖尿病发病时开始的胰岛素治疗可预防这些损伤。在逆转实验中，胰岛素治疗未能逆转已确立的迷宫学习缺陷，仅部分恢复了LTP。非空间预训练消除了糖尿病大鼠在空间版本迷宫中的行为缺陷。结论是，胰岛素治疗可能预防但不能逆转链脲佐菌素诱导的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空间版本中的行为缺陷与学习迷宫程序的困难有关，而非与空间学习受损有关。
