RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome.,Glia

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RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome.
Glia ( IF 5.4 ) Pub Date : 2020-01-16 , DOI: 10.1002/glia.23779
Eric D Hamlett ₁ , Erik Hjorth ₂ , Aurélie Ledreux ₃ , Anah Gilmore ₃ , Marianne Schultzberg ₂ , Ann Charlotte Granholm _{2,

3}

Affiliation

Inflammation can be resolved by pro-homeostatic lipids called specialized pro-resolving mediators (SPMs) upon activation of their receptors. Dysfunctional inflammatory resolution is now considered as a driver of chronic neuroinflammation and Alzheimer's disease (AD) pathogenesis. We have previously shown that SPM levels were reduced and also that SPM-binding receptors were increased in patients with AD compared to age-matched controls. Individuals with Down syndrome (DS) exhibit accelerated acquisition of AD neuropathology, dementia, and neuroinflammation at an earlier age than the general population. Beneficial effects of inducing resolution in DS have not been investigated previously. The effects of the SPM resolvin E1 (RvE1) in a DS mouse model (Ts65Dn) were investigated with regard to inflammation, neurodegeneration, and memory deficits. A moderate dose of RvE1 for 4 weeks in middle-aged Ts65Dn mice elicited a significant reduction in memory loss, along with reduced levels of serum pro-inflammatory cytokines, and reduced microglial activation in the hippocampus of Ts65Dn mice but had no effects in age-matched normosomic mice. There were no observable adverse side effects in Ts65Dn or in normosomic mice. These findings suggest that SPMs may represent a novel drug target for individuals with DS and others at risk of developing AD.

中文翻译：

RvE1 治疗可防止唐氏综合征 Ts65Dn 小鼠模型中的记忆丧失和神经炎症。

炎症可以通过称为特殊促分解介质 (SPM) 的促稳态脂质在其受体激活后得到解决。功能失调的炎症消退现在被认为是慢性神经炎症和阿尔茨海默病 (AD) 发病机制的驱动因素。我们之前已经表明，与年龄匹配的对照组相比，AD 患者的 SPM 水平降低并且 SPM 结合受体增加。患有唐氏综合症 (DS) 的个体在比一般人群更早的年龄表现出加速获得 AD 神经病理学、痴呆和神经炎症。以前没有研究过诱导 DS 消退的有益效果。研究了 SPM resolvin E1 (RvE1) 在 DS 小鼠模型 (Ts65Dn) 中对炎症、神经变性和记忆缺陷的影响。在中年 Ts65Dn 小鼠中，中等剂量的 RvE1 持续 4 周可显着减少记忆丧失，同时降低血清促炎细胞因子水平，并减少 Ts65Dn 小鼠海马中的小胶质细胞活化，但对年龄没有影响 -匹配的正常小鼠。在 Ts65Dn 或正常体小鼠中没有可观察到的不良副作用。这些发现表明，对于 DS 患者和其他有患 AD 风险的人来说，SPM 可能代表一种新的药物靶点。在 Ts65Dn 或正常体小鼠中没有可观察到的不良副作用。这些发现表明，对于 DS 患者和其他有患 AD 风险的人来说，SPM 可能代表一种新的药物靶点。在 Ts65Dn 或正常体小鼠中没有可观察到的不良副作用。这些发现表明，对于 DS 患者和其他有患 AD 风险的人来说，SPM 可能代表一种新的药物靶点。

更新日期：2020-01-16

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