期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 64, 期 2, 页码 379-392出版社
IOS PRESS
DOI: 10.3233/JAD-180230
关键词
Alzheimer's disease; CB2; endocannabinoid system; microglia; neuroinflammation
资金
- Deutsche Forschungsgemeinschaft (DFG) [FOR926 SP6, CP2]
- Boehringer Ingelheim Pharma GmbH Co.
- Medical Faculty of the University of Bonn Bonfor
It is widely accepted that the endocannabinoid system (ECS) is a modulator of neuroinflammation associated with neurodegenerative disorders, including Alzheimer's disease (AD). Thus, expression of the cannabinoid receptor 2 (CB2) is induced in plaque-associated microglia and astrocytes in brain tissues from AD patients and in genetic mouse models expressing pathogenic variants of the amyloid precursor protein (APP). However, the exact mechanism of CB2 signaling in this mouse model remains elusive, because the genetic deletion of CB2 and the pharmacological activation of CB2 both reduced neuroinflammation. Here, we demonstrate that CB2 deletion also improved cognitive and learning deficits in APP/PS1*CB2(-/-) mice. This was accompanied by reduced neuronal loss and decreased plaque levels and coincided with increased expression of A beta degrading enzymes. Interestingly, plaque-associated microglia in APP/PS1*CB2(-/-) mice showed a less activated morphology, while plaques were smaller and more condensed than in APP/PS1 mice. Taken together, these results indicate a beneficial effect of CB2-deficiency in APP transgenic mice. CB2 appears to be part of a protective system that may be detrimental when engaged continuously.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据