The anesthetic sevoflurane induces tau trafficking from neurons to microglia.

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.

• Authors: Yuanlin Dong, Feng Liang, Lining Huang, Fang Fang, Guang Yang, Rudolph E Tanzi, Yiying Zhang, Qimin Quan, Zhongcong Xie
• Journal: Communications biology (Commun Biol) Vol. 4 Issue 1 Pg. 560 (05 12 2021) ISSN: 2399-3642 [Electronic] England
• PMID: 33980987 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anesthetics, Inhalation
• Interleukin-6
• tau Proteins
• Sevoflurane

Topics

• Alzheimer Disease (metabolism)
• Anesthetics, Inhalation (pharmacology)
• Animals
• Brain (metabolism)
• Cognitive Dysfunction (chemically induced)
• Extracellular Vesicles (metabolism, physiology)
• Female
• Hippocampus (metabolism)
• Interleukin-6 (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Microglia (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Phosphorylation
• Protein Transport (drug effects, physiology)
• Sevoflurane (metabolism, pharmacology)
• Tauopathies (metabolism, physiopathology)
• tau Proteins (metabolism, physiology)