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The anesthetic sevoflurane induces tau trafficking from neurons to microglia
- Source :
- Communications Biology, Communications Biology, Vol 4, Iss 1, Pp 1-13 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Accumulation and spread of tau in Alzheimer’s disease and other tauopathies occur in a prion-like manner. However, the mechanisms and downstream consequences of tau trafficking remain largely unknown. We hypothesized that tau traffics from neurons to microglia via extracellular vesicles (EVs), leading to IL-6 generation and cognitive impairment. We assessed mice and neurons treated with anesthetics sevoflurane and desflurane, and applied nanobeam-sensor technology, an ultrasensitive method, to measure tau/p-tau amounts. Sevoflurane, but not desflurane, increased tau or p-tau amounts in blood, neuron culture medium, or EVs. Sevoflurane increased p-tau amounts in brain interstitial fluid. Microglia from tau knockout mice took up tau and p-tau when treated with sevoflurane-conditioned neuron culture medium, leading to IL-6 generation. Tau phosphorylation inhibitor lithium and EVs generation inhibitor GW4869 attenuated tau trafficking. GW4869 mitigated sevoflurane-induced cognitive impairment in mice. Thus, tau trafficking could occur from neurons to microglia to generate IL-6, leading to cognitive impairment.<br />Using their previously developed nanobeam-sensor technology to detect tau protein in the blood, Yuanlin Dong et al. find that the anaesthetic sevoflurane induces trafficking of tau from neurons to microglia in mice. They further see that microglia can take up tau, leading to Il-6 production, overall bringing new insights into the mechanism of sevoflurane-mediated cognitive impairment.
- Subjects :
- Male
0301 basic medicine
Lithium (medication)
QH301-705.5
Medicine (miscellaneous)
Mice, Transgenic
tau Proteins
Hippocampus
Article
General Biochemistry, Genetics and Molecular Biology
Sevoflurane
Extracellular Vesicles
Mice
03 medical and health sciences
Desflurane
0302 clinical medicine
Alzheimer Disease
Interstitial fluid
mental disorders
medicine
Animals
Cognitive Dysfunction
Biology (General)
Phosphorylation
Mice, Knockout
Neurons
Microglia
Interleukin-6
Chemistry
Brain
Alzheimer's disease
Mice, Inbred C57BL
Protein Transport
030104 developmental biology
medicine.anatomical_structure
nervous system
Tauopathies
Anesthetics, Inhalation
Anesthetic
Knockout mouse
Female
Neuron
General Agricultural and Biological Sciences
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 23993642
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Communications Biology
- Accession number :
- edsair.doi.dedup.....356a866bc165a10bb9648675d160d047