Biessels G J, Kamal A, Ramakers G M, Urban I J, Spruijt B M, Erkelens D W, Gispen W H
Rudolf Magnus Institute for Neurosciences, Utrecht, The Netherlands.
Diabetes. 1996 Sep;45(9):1259-66. doi: 10.2337/diab.45.9.1259.
Moderate impairment of learning and memory has been recognized as a complication of diabetes. The present study examined behavioral and electrophysiological measures of cerebral function in streptozotocin (STZ)-induced diabetic rats. Behavioral testing consisted of a spatial learning task in a water maze. Electrophysiological testing consisted of in vitro assessment of hippocampal long-term potentiation (LTP), an activity-dependent form of synaptic plasticity, which is believed to be related to the cellular mechanisms of learning and memory. Two experiments were performed: the first with severely hyperglycemic rats and the second with moderately hyperglycemic rats. Rats were tested in the water maze 11 weeks after induction of diabetes. Next, LTP was measured in vitro in trained animals. Both spatial learning and LTP expression in the CA1 field of the hippocampus were impaired in severely hyperglycemic rats as compared with nondiabetic controls. In contrast, spatial learning and hippocampal LTP were unaffected in moderately hyperglycemic rats. The association of alterations in hippocampal LTP with specific learning impairments has previously been reported in conditions other than diabetes. Our findings suggest that changes in LTP-like forms of synaptic plasticity in the hippocampus, and possibly in other cerebral structures, are involved in learning deficits in STZ-induced diabetes. The beneficial effect of moderate glycemic control on both place learning and hippocampal LTP supports the significance of the relation between these two parameters and indicates that the development of the observed deficits may be related to the level of glycemic control.
学习和记忆的中度损害已被认为是糖尿病的一种并发症。本研究检测了链脲佐菌素（STZ）诱导的糖尿病大鼠脑功能的行为学和电生理学指标。行为测试包括在水迷宫中的空间学习任务。电生理学测试包括对海马体长期增强（LTP）的体外评估，LTP是一种与活动相关的突触可塑性形式，被认为与学习和记忆的细胞机制有关。进行了两个实验：第一个实验用的是严重高血糖大鼠，第二个实验用的是中度高血糖大鼠。在诱导糖尿病11周后对大鼠进行水迷宫测试。接下来，在经过训练的动物身上体外测量LTP。与非糖尿病对照组相比，严重高血糖大鼠在海马体CA1区的空间学习和LTP表达均受损。相比之下，中度高血糖大鼠的空间学习和海马体LTP未受影响。此前在糖尿病以外的其他情况下，已有关于海马体LTP改变与特定学习障碍之间关联的报道。我们的研究结果表明，海马体以及可能其他脑结构中类似LTP的突触可塑性变化与STZ诱导的糖尿病中的学习缺陷有关。适度血糖控制对位置学习和海马体LTP均有有益作用，这支持了这两个参数之间关系的重要性，并表明观察到的缺陷的发展可能与血糖控制水平有关。
