Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Professor Lineu Prestes, 1524, São Paulo, SP, 05508-900, Brazil.
Physiol Behav. 2012 Oct 10;107(3):401-13. doi: 10.1016/j.physbeh.2012.06.019. Epub 2012 Aug 16.
Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-Jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes.
脑内葡萄糖代谢和胰岛素信号转导紊乱被认为是阿尔茨海默病的一个可能病因。本研究旨在探讨脑室注射链脲佐菌素（STZ）诱导的大鼠认知障碍的时间过程，并将其与随后的神经退行性过程相关联。通过使用 Morris 水迷宫任务的参考记忆和工作记忆版本以及免疫印迹和 Fluoro-Jade C 组织化学评估神经退行性标记物，评估了 STZ 的早期和晚期效应。结果显示出不同类型的行为和神经退行性反应，具有不同的时间过程。我们观察到 STZ 注射后 3 小时即出现工作记忆早期破坏，随后在 STZ 注射后 1 天和 15 天出现海马神经退行性过程。记忆破坏随着时间的推移而增加，并最终导致不同脑结构中淀粉样β肽和过度磷酸化 Tau 蛋白水平的显著变化。这些发现增加了关于阿尔茨海默病样 STZ 动物模型和神经退行性过程背后机制的信息。
