Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment
| Autor: | Zhou Liu, Shouchao Wei, Li Hu, Chenyao Kang, Zhiyou Cai, Shaoping Zhu, Zhuangsheng Wei, Wanjuan Peng, Haihong Zhou, Bin Zhao, Kanglan Li, Yingren Mai, Wei Wei, Wanxin Jie, Ruikai Li |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology Clinical Biochemistry Hippocampus tau Proteins Blood–brain barrier Proinflammatory cytokine Extracellular Vesicles Feces 03 medical and health sciences Cognition 0302 clinical medicine Memory Morris Water Maze Test GSK-3 medicine Animals Humans Cognitive Dysfunction Secretion Phosphorylation Aged Glycogen Synthase Kinase 3 beta Behavior Animal Microglia Chemistry Vesicle Brain Cell Biology Middle Aged Gastrointestinal Microbiome Cell biology Mice Inbred C57BL Disease Models Animal Bacterial Outer Membrane 030104 developmental biology medicine.anatomical_structure Case-Control Studies 030220 oncology & carcinogenesis Cytokines Female Bacterial outer membrane |
| Zdroj: | Journal of Cellular Physiology. 235:4843-4855 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.29362 |
| Popis: | Outer membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well-known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood-brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK-3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin-1β, and tumour necrosis factor-α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK-3β pathway and finally leading to cognitive impairment. |
| Databáze: | OpenAIRE |
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