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A Novel Derivative of Xanomeline EUK1001 Improved Neurogenesis in Mice

Author: ZhangXiaoLiang
Tutor: HuYingHe
School: East China Normal University
Course: Genomics
Keywords: M1 receptor EUK1001 Nerve regeneration BrdU Quantitative PCR BDNF
CLC: Q42
Type: Master's thesis
Year: 2010
Downloads: 10
Quote: 0
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Abstract

Cholinergic system involved in the play of the cognitive function and neurogenesis regulation, and is closely related to the pathological process of AD. , M1 receptor expression in the forebrain and hippocampus, cushions promise Merrill (Xanomeline), its agonist can improve cognitive function and alleviate AD pathological symptoms, has entered clinical trials has been shown that, due to Severe peripheral side effects limit its clinical application. In the laboratory's previous studies found that The new cushions promise Merrill Lynch the derivatives EUK1001 can improve learning and memory of aged mice and can enhance synaptic plasticity in the hippocampus. And it is worth noting that compared cushions promise Merrill Lynch, EUK1001 has more side effects. EUK1001 can improve learning and memory function in mice and enhance the relationship between the synaptic plasticity of the brain, as well as cognitive function and neurogenesis, EUK1001 may also affect neurogenesis in adult mice. To test this possibility, C57BL/6J mice were given the 15 days EUK1001 processing, injection of thymidine analogues BrdU labeled newborn nerve cells by immunohistochemistry and nerve cell differentiation and maturation of the various stages of the unique biomarkers analysis, detection of the changes generated by the mouse neural. Found EUK1001 treatment promotes the proliferation of neural precursor cells in the hippocampus of mice with the survival of newborn nerve cells, but their differentiation was no significant impact, no apparent effect of the lateral ventricle subependymal neurogenesis. In order to initially explored EUK1001 processing mechanism to promote the proliferation of nerve cells, selected six reported in the literature and adult nervous generate gene expression in the mouse hippocampus, the real-time PCR analysis. The results show that the EUK1001 treatment significantly increased the expression level of BDNF in the hippocampus, but for other related gene expression was not significantly affected. This prompted out EUK1001 possible by increasing the expression of BDNF, thus contributing to the proliferation of hippocampal neurons. The study showed that the mice were given the 15 days EUK1001 treatment could upregulate the expression of BDNF mRNA in the hippocampus, and promote the proliferation and survival of hippocampal neurons, which may be the basis of the improvement of cognitive ability in mice. Compared with known M1 receptor agonist cushions promise Merrill, EUK1001 has significantly enhanced the role of memory and smaller peripheral side effects, shows the potential for drug development in the treatment of AD or age-related cognitive impairment.

A Novel Derivative of Xanomeline EUK1001 Improved Neurogenesis in Mice

Abstract

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