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目的为了分析EUK1001- 新的呫诺美林衍生物的功能性质,本实验以老年小鼠为实验材料,研究了该化合物的急性毒理以及对突触可塑性和识别记忆的影响。方法通过口服及腹腔注射途径,对小鼠进行梯度剂量的毒理学实验,测定EUK1001的半致死剂量(median lethal dose, LD50); 采用新奇物体识别任务和离体脑片电生理学技术研究EUK1001对老年小鼠识别记忆和海马突触可塑性的影响。结果 EUK1001 比呫诺美林呈现出更小的毒副作用。在新奇事物识别实验中,EUK1001 能够显著改善老年小鼠在识别记忆任务中的表现。此外,海马脑片灌流1 μmol/L的EUK1001,能直接诱导产生长时程突触增强(long-term potentiation)。结论 EUK1001能够改善正常老龄化过程中学习记忆能力的衰退。
OBJECTIVE To analyze the functional properties of EUK1001-a new xanomeline derivative, we investigated the acute toxicology of the compound and its effect on synaptic plasticity and memory recognition in aged mice. METHODS: Gradient dose toxicology experiments were performed in mice by oral and intraperitoneal injection to determine the median lethal dose (LD50) of EUK1001. The novelty object recognition task and in vitro brain slice electrophysiology were used to study the effects of EUK1001 on aging Mouse recognition memory and hippocampal synaptic plasticity. EUK1001 showed less toxic side effects than xanomeline. In novelty recognition experiments, EUK1001 can significantly improve the performance of older mice in recognizing memory tasks. In addition, perfusion of 1 μmol / L EUK1001 in the hippocampal slices directly induced long-term potentiation. Conclusions EUK1001 can ameliorate the decline of learning and memory abilities during normal aging.