Duelli R, Schröck H, Kuschinsky W, Hoyer S
Department of Physiology, University of Heidelberg, Germany.
Int J Dev Neurosci. 1994 Dec;12(8):737-43. doi: 10.1016/0736-5748(94)90053-1.
The purpose of the present study was to investigate whether or not cerebral glucose utilization is changed locally after damage of the neuronal insulin receptor by means of intracerebroventricular (icv) streptozotocin (STZ) administered in a subdiabetogenic dosage (1.5 mg/kg bw.). STZ was administered at the start of the study, and 2 and 21 days later bilaterally into the cerebral ventricles in rats of a mean age of 18 months. The local distribution of cerebral glucose utilization was analyzed in conscious rats on the 42nd day after the first STZ injection using the quantitative (14C)-2-deoxyglucose method. Of the 35 brain structures investigated from autoradiograms of brain sections, 17 showed a reduction in glucose utilization. Decreases in glucose utilization were observed in the frontal, parietal, sensory motor, auditory and entorhinal cortex and in all hippocampal subfields. In contrast, glucose utilization was increased in two white matter structures. The decrease in cerebral glucose utilization observed in cortical and hippocampal areas in the present study may correspond to changes in morphobiological parameters which have been found in patients with Alzheimer's disease. The present data are in accordance with the hypothesis that an impairment in the control of neuronal glucose metabolism at the insulin receptor site may exist in sporadic dementia of Alzheimer type (DAT), and can be studied by the icv STZ animal model.
本研究的目的是通过以亚致糖尿病剂量（1.5毫克/千克体重）脑室内注射链脲佐菌素（STZ），来研究神经元胰岛素受体受损后大脑局部葡萄糖利用是否发生变化。在研究开始时、2天和21天后，对平均年龄为18个月的大鼠双侧脑室注射STZ。在首次注射STZ后第42天，使用定量（14C）-2-脱氧葡萄糖法分析清醒大鼠大脑葡萄糖利用的局部分布。在从脑切片放射自显影片上研究的35个脑结构中，17个显示葡萄糖利用减少。在额叶、顶叶、感觉运动区、听觉和内嗅皮质以及所有海马亚区均观察到葡萄糖利用减少。相比之下，两个白质结构中的葡萄糖利用增加。本研究中在皮质和海马区观察到的大脑葡萄糖利用减少可能与在阿尔茨海默病患者中发现的形态生物学参数变化相对应。目前的数据符合这样的假设，即散发性阿尔茨海默型痴呆（DAT）可能存在胰岛素受体部位神经元葡萄糖代谢控制受损的情况，并且可以通过脑室内注射STZ动物模型进行研究。
