Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H b-synuclein
Ibuprofen ameliorates protein aggregation and astrocytic gliosis, but not cognitive dysfunction, in a transgenic mouse expressing dementia with Lewy bodies-linked P123H b-synuclein
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在表达路易体相关 P123H b-突触核蛋白痴呆的转基因小鼠中，布洛芬可改善蛋白质聚集和星形胶质细胞增生，但不能改善认知功能障碍
DOI：
10.1016/j.neulet.2012.03.037
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发表时间：
2012
期刊：
影响因子：
2.5
通讯作者：
Hashimoto M
中科院分区：
文献类型：
--
作者：
S ekiyama K;Fujita M;Sekigawa A;Takamatsu Y;Waragai M;Takenouchi T;Sugama S;Hashimoto M
流行病学研究表明，布洛芬，一种非甾体抗炎药，降低神经退行性疾病的风险，如阿尔茨海默病（AD）和帕金森病（PD）。在这种情况下，已经表明，布洛芬的长期治疗改善了AD小鼠模型的认知功能障碍和组织病理学结果。然而，布洛芬在PD和相关突触核蛋白病如路易体痴呆（DLB）的动物模型中的治疗作用尚未研究。因此，本研究的主要目的是确定布洛芬是否改善表达DLB-连锁P123 H β-突触核蛋白的转基因（tg）小鼠的神经病理学和认知功能障碍。P123 H β-突触核蛋白tg小鼠及其3个月龄的非tg同窝小鼠在其饮食中给予布洛芬（n = 13）。对照组未接受布洛芬（n = 11）。3个月后，使用Morris水迷宫测试评估小鼠，然后进行神经病理学分析。与对照P123 H β-突触核蛋白tg小鼠相比，接受布洛芬的P123 H β-突触核蛋白tg小鼠的蛋白质聚集和星形胶质细胞增生显著减少。然而，布洛芬治疗对P123 H β-synuclein tg小鼠在Morris水迷宫测试中的学习障碍几乎没有改善。这些结果表明，布洛芬改善神经病理不一定导致突触核蛋白病如DLB的认知功能改善。
Epidemiological studies have shown that ibuprofen, a non-steroidal anti-inflammatory drug, reduces the risk for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this context, it has been shown that chronic treatment with ibuprofen improves cognitive dysfunction and histopathologic outcome in mouse models of AD. However, the therapeutic effects of ibuprofen in animal models of PD and related synucleinopathies such as dementia with Lewy bodies (DLB) have not been investigated. Therefore, the main objective of this study was to determine if ibuprofen ameliorates neuropathology and cognitive dysfunction in a transgenic (tg) mouse expressing DLB-linked P123H β-synuclein. P123H β-synuclein tg mice and their non-tg littermates aged 3 months were given ibuprofen in their diet (n=13). Controls did not receive ibuprofen (n=11). After 3 months, the mice were evaluated using a Morris water maze test, followed by neuropathological analyses. Compared to control P123H β-synuclein tg mice, P123H β-synuclein tg mice that received ibuprofen had significantly reduced protein aggregation and astrogliosis. However, ibuprofen treatment produced little improvement of the learning disability of P123H β-synuclein tg mice in the Morris water maze test. These results suggest that amelioration of neuropathologies by ibuprofen does not necessarily lead to improved cognitive function in synucleinopathies such as DLB.