The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain. Increased calcium level may correlate with endoplasmic reticulum (ER) stress and significantly increased expression of ER stress markers like GRP78, GADD and caspase-12 were observed in STZ treated rat brain. Cellular communication was also affected by STZ administration as observed by increased expression connexin 43. With this view the activation of astrocytes and microglia was also assessed and observed by augmented GFAP and cd11b expression which were partially inhibited with donepezil treatment. The significantly increased level of degenerating neurons, caspase-3 and DNA fragmentation was also observed in rat brain regions which were not inhibited with donepezil treatment and validating the clinical observations. In conclusion, study indicated the STZ induced occurrence of Alzheimer's pathology. Further, STZ administration also caused depleted glucose level, inhibited mitochondrial activity, augmented calcium levels, ER stress, altered cellular communication and neuronal death which were partially attenuated with donepezil treatment.

中文翻译：

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葡萄糖相关的能量危机和内质网应激的参与：链脲佐菌素的诱导诱发阿尔茨海默氏样病理。

进行本研究是为了利用链脲佐菌素（STZ）诱导的实验大鼠模型来关联阿尔茨海默氏病病理学中的细胞和分子变化。使用立体定向手术，然后通过多奈哌齐给药，通过脑室内途径双侧在大鼠脑中施用STZ。服用STZ后观察到了阿尔茨海默氏症相关的病理学标记，例如乙酰胆碱酯酶（AChE）活性，tau磷酸化和淀粉样蛋白聚集。STZ治疗显示大鼠大脑皮层和海马区的葡萄糖和葡萄糖转运蛋白（GLUT）含量降低，钙水平升高。钙水平升高可能与内质网（ER）应激相关，并显着增加ER应激标志物（例如GRP78）的表达，在STZ处理的大鼠脑中观察到GADD和caspase-12。如通过表达连接蛋白43增加所观察到的，STZ施用也影响细胞通讯。通过这种观点，还通过增强的GFAP和cd11b表达来评估和观察星形胶质细胞和小胶质细胞的活化，而多奈哌齐治疗则部分抑制了它们的表达。在大鼠脑区域也观察到了退化神经元，caspase-3和DNA片段的显着增加，而多奈哌齐治疗并没有抑制这种现象，并验证了临床观察结果。总之，研究表明STZ诱发了阿尔茨海默氏病的发生。此外，服用STZ还会导致葡萄糖水平降低，线粒体活性受到抑制，钙水平升高，内质网应激，