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Logo of neuroscibullNeuroscience Bulletin
 
Neurosci Bull. 2008 August; 24(4): 251.
Published online 2008 August 2. doi:  10.1007/s12264-008-0204-5
PMCID: PMC5552585

Language: English | Chinese

A novel derivative of xanomeline improved memory function in aged mice

一种新的呫诺美林衍生物改善老年小鼠的记忆能力

Abstract

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 EUK1001 were evaluated.

Methods

To examine the median lethal dose (LD50) of EUK1001, a wide dose range of EUK1001 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 agerelated cognitive deficits.

Keywords: xanomeline, EUK1001, LD50, hippocampus, long-term potentiation, memory

摘要

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。

关键词: 呫诺美林, EUK1001, 半致死剂量, 海马, 长时程增强, 记忆

Footnotes

The two authors contributed equally to this work.

References

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Articles from Neuroscience Bulletin are provided here courtesy of Springer