Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of strepozotocin-induced diabetic rats
Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of strepozotocin-induced diabetic rats
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DOI：
10.1016/s0306-4522(02)00874-6
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Ramakers, GMJ
中科院分区：
文献类型：
--
作者：
Kamal, A;Artola, A;Ramakers, GMJ
在人类和动物模型中，糖尿病都与认知功能受损有关。在糖尿病大鼠中，认知缺陷与海马区活动依赖型突触可塑性的变化有关。人们注意到与正常脑老化的病理生理学有许多相似之处，并出现了一种观点，即糖尿病对大脑的影响最好被描述为“加速脑老化”。在本研究中，我们研究了链脲佐菌素诱导的糖尿病大鼠的CA1锥体神经元是否表现出增加的缓慢后超极化，这通常被认为是神经元老化的标志。链脲佐菌素诱导的糖尿病大鼠CA1区锥体神经元的静息膜电位、输入电阻、膜时间常数、动作电位幅度和时程与年龄匹配的对照组大鼠无差异。然而，在一系列动作电位中，糖尿病动物的动作电位有更多的加宽，即所谓的“棘波加宽”。在糖尿病动物中，由一系列动作电位引起的缓慢后超极化的幅度确实增加了。有趣的是，当钙离子尖峰引起缓慢的后超极化时，对照组和糖尿病大鼠之间没有差异。这表明糖尿病患者慢后超极化的增加可能是由于尖峰增宽导致的钙内流增加所致。这些数据强调了这样一种观点，即糖尿病大脑在神经元水平上与大脑老化具有共同的特性。(C)2003年IBRO。爱思唯尔科学有限公司出版。版权所有。
Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca2+ spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca2+ influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.