Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer's disease mouse model
Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer's disease mouse model
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DOI：
10.1016/j.neurobiolaging.2014.09.019
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发表时间：
2015-02-01
影响因子：
4.2
通讯作者：
Zimmer, Andreas
中科院分区：
文献类型：
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作者：
Schmoele, Anne-Caroline;Lundt, Ramona;Zimmer, Andreas
一些研究表明，大麻素受体2（CB 2）在与阿尔茨海默病（AD）进展相关的神经炎症中起着重要作用。本研究探讨了CB 2在体外小胶质细胞活化中的作用，以及在AD转基因小鼠模型（APP/PS1小鼠）中表征神经炎症过程。基于细胞表面ICAM和CD 40的表达以及趋化因子和细胞因子CCL 2、IL-6和TNF α的释放，我们证明从CB 2（-/-）小鼠收获的小胶质细胞对促炎刺激的反应比CB 2（+/+）小胶质细胞低。缺乏CB 2的转基因APP/PS1小鼠显示小胶质细胞和浸润性巨噬细胞的百分比降低。此外，他们还显示了脑中促炎趋化因子和细胞因子的表达水平降低，以及可溶性A β 40/42浓度降低。神经炎症的减少不影响APP/PS1* CB 2（-/-）小鼠的空间学习和记忆。这些数据表明CB 2在阿尔茨海默病相关神经炎症中的作用，独立于影响Ab介导的病理和认知障碍。(C)2015爱思唯尔公司All rights reserved.
Several studies have indicated that the cannabinoid receptor 2 (CB2) plays an important role in neuroinflammation associated with Alzheimer's disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model of AD (APP/PS1 mice). We demonstrate that microglia harvested from CB2(-/-) mice were less responsive to pro-inflammatory stimuli than CB2(+/+) microglia, based on the cell surface expression of ICAM and CD40 and the release of chemokines and cytokines CCL2, IL-6, and TNF alpha. Transgenic APP/PS1 mice lacking CB2 showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokines in the brain, as well as diminished concentrations of soluble A beta 40/42. The reduction in neuroinflammation did not affect spatial learning and memory in APP/PS1*CB2(-/-) mice. These data suggest a role for the CB2 in Alzheimer's disease-associated neuroinflammation, independent of influencing Ab-mediated pathology and cognitive impairment. (C) 2015 Elsevier Inc. All rights reserved.