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mdx 小鼠的神经认知障碍。

Neurocognitive Impairment in mdx Mice.

机构信息

Research Group on Neurodevelopment of Childhood and Adolescence, Laboratory of Experimental Neuroscience, Postgraduate Program in Health Sciences, University of South Santa Catarina, Palhoça, SC, Brazil.

Laboratory of Epidemiology, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil.

出版信息

Mol Neurobiol. 2019 Nov;56(11):7608-7616. doi: 10.1007/s12035-019-1573-7. Epub 2019 May 10.

DOI:10.1007/s12035-019-1573-7
PMID:31077034
Abstract

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that affects muscles and also the brain, resulting in memory and behavioral problems. In the pathogenesis of DMD, inflammation is an important factor during the degenerative process. However, the involvement of the brain is still unclear. Therefore, the objective of this study is to evaluate the cognitive involvement, BDNF levels, cytokine levels through the levels of TNF-α and IL-1β, the myeloperoxidase (MPO) activity, and the expression of proteins postsynaptic density (PSD)-95 and synaptophysin in the brain of mdx mice. To this aim, we used adult mdx mice. It was observed that mdx mice presented deficits on the habituation, aversive, and object recognition memory. These animals also had a depression-like behavior and an anxiety-like behavior, a decrease of BDNF levels, an increase in the levels of TNF-α and IL-1β, an increase of MPO activity, and an overexpression of synaptophysin and PSD-95 in brain tissue. In conclusion, these data show that mdx mice possibly present a neuroinflammatory component and the involvement of synaptic proteins associated to memory storage and restoring process impairment as well as a depressive- and anxiety-like behavior.

摘要

杜氏肌营养不良症(DMD)是一种影响肌肉和大脑的神经肌肉疾病,导致记忆和行为问题。在 DMD 的发病机制中,炎症是退行性过程中的一个重要因素。然而,大脑的参与仍不清楚。因此,本研究的目的是评估认知障碍、BDNF 水平、细胞因子水平(通过 TNF-α 和 IL-1β 水平)、髓过氧化物酶(MPO)活性以及脑内突触后密度(PSD)-95 和突触小体蛋白的表达在 mdx 小鼠的大脑中的作用。为此,我们使用了成年 mdx 小鼠。结果表明,mdx 小鼠在习惯化、厌恶和物体识别记忆方面存在缺陷。这些动物还表现出类似抑郁和焦虑的行为,BDNF 水平降低,TNF-α 和 IL-1β 水平升高,MPO 活性增加,脑组织中突触小体蛋白和 PSD-95 过度表达。总之,这些数据表明 mdx 小鼠可能存在神经炎症成分,以及与记忆储存和恢复过程受损以及类似抑郁和焦虑的行为相关的突触蛋白的参与。

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本文引用的文献

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PLoS One. 2018 Mar 30;13(3):e0194636. doi: 10.1371/journal.pone.0194636. eCollection 2018.
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Global muscular dystrophy research: A 25-year bibliometric perspective.
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