Intracerebroventricular (icv) administration of streptozotocin (STZ) has been used as a metabolic model of sporadic Alzheimer's disease (AD). Erythropoietin (EPO) possesses neuroprotective and memory-improving effects, which might be advantageous in treating different characteristics of AD. Nevertheless, the hematopoietic effect of EPO has hindered its application as a neuroprotective agent. Previous studies have shown that a new Epo derivative called carbamylated Erythropoietin-Fc (CEPO-Fc), yield noticeable neuroprotective effects without affecting hematopoiesis. In this study, the neuroprotective effects of CEPO-Fc on icv-STZ induced memory impairment and hippocampal apoptosis were examined. Adult male Wistar rats weighing 250-300 g were used. STZ was administered on days 1 and 3 (3 mg/kg in divided doses/icv), and CEPO-Fc was administered at the dose of 5000 IU/ip/daily during days 4-14. The animals were trained in Morris water maze during days 15-17, and the memory retention test was performed on the 18th day. Following behavioral studies, the animals were sacrificed and their hippocampi isolated to determine the amounts of cleaved caspase-3 (the landmark of apoptosis). The results showed that CEPO-Fc treatment at the dose of 5000 IU/kg/ip was able to prevent the learning and memory deficit induced by icv-STZ. Western blot analysis revealed that STZ prompted the cleavage of caspase-3 in the hippocampus while pretreatment with CEPO-Fc significantly reduced the cleavage of this protein. Collectively, our findings suggest that CEPO-Fc could restore STZ-induced learning and memory impairment as well as apoptosis in the hippocampal region in a rat model of sporadic AD induced by icv-STZ.

中文翻译：

---

氨基甲酸酯化的促红细胞生成素Fc融合蛋白（CEPO-Fc）对大鼠脑室内给予链脲佐菌素诱导的学习和记忆障碍及海马凋亡的影响。

脑室内（icv）链脲佐菌素（STZ）的给药已被用作散发性阿尔茨海默氏病（AD）的代谢模型。促红细胞生成素（EPO）具有神经保护和记忆改善作用，可能在治疗AD的不同特征方面具有优势。然而，EPO的造血作用阻碍了其作为神经保护剂的应用。先前的研究表明，一种新的Epo衍生物，称为氨基甲酸酯化的促红细胞生成素-Fc（CEPO-Fc），在不影响造血作用的情况下可产生明显的神经保护作用。在这项研究中，检查了CEPO-Fc对icv-STZ诱导的记忆障碍和海马细胞凋亡的神经保护作用。使用重250-300g的成年雄性Wistar大鼠。STZ在第1天和第3天服用（3 mg / kg，分次剂量/ icv），在第4-14天期间，每天以5000 IU / ip / ip的剂量给予CEPO-Fc。在第15-17天在Morris水迷宫中对动物进行训练，并在第18天进行记忆保留测试。进行行为研究后，处死动物并分离海马，以确定裂解的caspase-3的量（凋亡的标志）。结果表明，以5000 IU / kg / ip的剂量使用CEPO-Fc能够预防icv-STZ引起的学习和记忆障碍。蛋白质印迹分析表明，STZ促进了海马caspase-3的裂解，而用CEPO-Fc预处理则显着降低了该蛋白的裂解。总的来说，