CAJ | 학술논문

目的为了分析EUK1001-新的咕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比咕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.
목적 위료분석EUK1001-신적구낙미림연생물적공능성질,본실험이노년소서위실험재료,연구료해화합물적급성독리이급대돌촉가소성화식별기억적영향.방법 통과구복급복강주사도경,대소서진행제도제량적독이학실험,측정EUK1001적반치사제량(median lethal dose,LD50);채용신기물체식별임무화리체뇌편전생이학기술연구EUK1001대노년소서식별기억화해마돌촉가소성적영향.결과 EUK1001비구낙미림정현출경소적독부작용.재신기사물식별실험중,EUK1001능구현저개선노년소서재식별기억임무중적표현.차외,해마뇌편관류1 μmol/L적EUK1001,능직접유도산생장시정돌촉증강(long-term potentiation).결론 EUK1001능구개선정상노령화과정중학습기억능력적쇠퇴.
Objective To characterize the function of a new xanomeline-derived M1 agonist, 3-[3-(3-florophenyl-2-propyn- 1- ylthio)-1,2,5-thiadiazol-4-yl]- 1,2,5,6- tetrahydro-1-methylpyridine Oxalate (EUK1001 ), the acute toxicity and the effects on synaptic plasticity and cognition of EUKI001 were evaluated. Methods To examine the median lethal dose (LD50) of EUK 1001, a wide dose range of EUK 1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. Results EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion We conclude that EUK1001 can improve the age- related cognitive deficits.