摘要
背景:微剂量锂对阿尔茨海默病(AD)有保护作用,但其保护作用的确切机制尚不清楚。 目的:为了进一步研究Aβ早期病理过程中的作用,我们评价了微量锂制剂NP 03是否对Aβ介导的氧化损伤和神经感染有调节作用。应用于高表达淀粉样前体蛋白(APP)的AD样淀粉样变转基因大鼠模型。 方法:将转基因大鼠和野生型白蚁用NP 03或载体制剂治疗8周,从3个月开始,在t期出现β斑块沉积前的一个阶段。转基因老鼠。 结果:氧化和亚硝基应激标记物、蛋白质结合的4-羟基壬烯醛(Hne)和蛋白-3-硝基酪氨酸(3-nt)、炎性细胞因子的产生以及小胶质细胞的合成。对β负荷神经元进行检测。NP 03能显著降低McGill-R-Thy1-app转基因大鼠脑内HNE和3-NT的含量,减少促炎细胞因子的产生。NP 03进一步r诱导海马CA1区小胶质细胞表面受体TREM 2的表达,导致海马CA1区小胶质细胞向β负荷神经元的募集相应减少。 结论:NP 03可能通过改善氧化/亚硝基损伤和神经炎症而延缓AD样病变,增加了低剂量o的可能性。F微囊化锂在早期或临床前AD中可能具有治疗性预防价值.
关键词: 阿尔茨海默病,氧化应激,炎症,微量锂,小胶质细胞,TREM 2。
Current Alzheimer Research
Title:Microdose Lithium NP03 Diminishes Pre-Plaque Oxidative Damage and Neuroinflammation in a Rat Model of Alzheimer’s-like Amyloidosis
Volume: 15 Issue: 13
关键词: 阿尔茨海默病,氧化应激,炎症,微量锂,小胶质细胞,TREM 2。
摘要: Background: Microdose lithium is protective against Alzheimer’s disease (AD), although the precise mechanisms through which its protective effects are conferred remain unclear.
Objective: To further examine the effects during the earliest stages of Aβ pathology, we evaluated whether NP03, a microdose lithium formulation, modulates Aβ-mediated oxidative damage and neuroinflammation when applied to a rat transgenic model of AD-like amyloidosis overexpressing amyloid precursor protein (APP).
Method: McGill-R-Thy1-APP transgenic rats and wild-type littermates were treated with NP03 or vehicle formulation for 8 weeks beginning at 3 months of age - a phase preceding Aβ plaque deposition in the transgenic rats.
Results: Oxidative and nitrosative stress markers, protein-bound 4-hydroxynonenal (HNE) and proteinresident 3-nitrotyrosine (3-NT), inflammatory cytokines production, as well as microglial recruitment towards Aβ-burdened neurons were assayed. NP03 significantly decreased cerebral HNE and 3-NT, and reduced production of pro-inflammatory cytokines in McGill-R-Thy1-APP transgenic rats. NP03 further reduced expression of microglia surface receptor Trem2 and led to a corresponding reduction in microglia recruitment towards Aβ-burdened neurons in the CA1 region of the hippocampus.
Conclusion: These results suggest that NP03 may function to slow the AD-like pathology in part by modifying oxidative/nitrosative damage and neuroinflammation, raising the possibility that low doses of microencapsulated lithium might be of therapeutic-preventive value during very early or preclinical AD.
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Microdose Lithium NP03 Diminishes Pre-Plaque Oxidative Damage and Neuroinflammation in a Rat Model of Alzheimer’s-like Amyloidosis, Current Alzheimer Research 2018; 15 (13) . https://dx.doi.org/10.2174/1567205015666180904154446
DOI https://dx.doi.org/10.2174/1567205015666180904154446 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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