Long-Term DL-3-n-Butylphthalide Treatment Alleviates Cognitive Impairment Correlate With Improving Synaptic Plasticity in SAMP8 Mice.
Long-Term DL-3-n-Butylphthalide Treatment Alleviates Cognitive Impairment Correlate With Improving Synaptic Plasticity in SAMP8 Mice.
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DOI：
10.3389/fnagi.2018.00200
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发表时间：
2018
影响因子：
4.8
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Lv C;Ma Q;Han B;Li J;Geng Y;Zhang X;Wang M
阿尔茨海默病（AD）是世界范围内最普遍的痴呆形式。AD的特征是在发病时轻度认知损害，随着年龄的增长不可逆地进展到晚期的严重神经变性和认知缺陷。不幸的是，没有有效的治疗方法来预防或延迟AD的认知症状。研究表明，DL-3-正丁基苯酞（DL-NBP）通过减少氧化应激、抑制细胞凋亡和减少tau蛋白磷酸化来减轻小鼠中由淀粉样蛋白-β诱导的认知障碍。在这项研究中，我们研究了DL-NBP管理对衰老加速小鼠倾向8（SAMP 8）模型的年龄相关性痴呆的认知功能的影响。DL-NBP治疗3个月减轻了SAMP 8小鼠的认知障碍，如通过Morris水迷宫测试中的表现所评估的。此外，DL-NBP显着增加突触素和突触后密度蛋白95在SAMP 8小鼠海马中的表达，表明对海马结构突触可塑性的保护作用。此外，脑源性神经营养因子/原肌球蛋白受体激酶B信号，以前显示，以促进突触可塑性，显着增强DL-NBP管理。我们的研究结果表明，DL-NBP是一个潜在的候选药物治疗AD的认知功能障碍，并可能作为进一步研究AD药物的开发的基础。
Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. AD is characterized by mild cognitive impairment at onset, irreversibly progressing with age to severe neurodegeneration and cognitive deficits in the late stages. Unfortunately, no effective treatments exist to prevent or delay the cognitive symptoms of AD. Studies have shown that DL-3-n-butylphthalide (DL-NBP) alleviates cognitive impairment induced by amyloid-β in mice by reducing oxidative stress, inhibiting apoptosis, and decreasing tau phosphorylation. In this study, we examined the effects of DL-NBP administration on cognitive function in the senescence-accelerated mouse prone 8 (SAMP8) model of age-related dementia. DL-NBP treatment for 3 months alleviated cognitive impairment in SAMP8 mice as assessed by performance in the Morris water maze test. Moreover, DL-NBP significantly increased the expression of synaptophysin and postsynaptic density protein 95 in the hippocampus of SAMP8 mice, indicative of a protective effect on hippocampal structural synaptic plasticity. In addition, brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling, previously shown to promote synaptic plasticity, was significantly enhanced by the DL-NBP administration. Our findings suggest that DL-NBP is a potential drug candidate for the treatment of cognitive impairment in AD and may serve as the foundation for further research into the development of AD drugs.
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DOI：
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影响因子：
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