Brain, Behavior, & Immunity - Health (Oct 2020)

Interaction of Tau, IL-6 and mitochondria on synapse and cognition following sevoflurane anesthesia in young mice

  • Jie Zhang,
  • Yuanlin Dong,
  • Lining Huang,
  • Xiaoming Xu,
  • Feng Liang,
  • Sulpicio G. Soriano,
  • Yiying Zhang,
  • Zhongcong Xie

Journal volume & issue
Vol. 8
p. 100133

Abstract

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Tau phosphorylation is associated with cognitive impairment in young mice. However, the underlying mechanism and targeted interventions remain mostly unknown. We set out to determine the potential interactions of Tau, interleukin 6 (IL-6) and mitochondria following treatment of anesthetic sevoflurane and to assess their influences on synapse number and cognition in young mice. Sevoflurane (3% for 2 ​h) was given to wild-type, Tau knockout, IL-6 knockout, and cyclophilin D (CypD) knockout mice on postnatal (P) day 6, 7 and 8. We measured amounts of phosphorylated Tau, IL-6, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, postsynaptic density 95 (PSD-95), synaptophysin, N-cadherin, synapse number, and cognitive function in the mice, employing Western blot, electron microscope and Morris water maze among others. Here we showed that sevoflurane increased Tau phosphorylation and caused IL-6 elevation, mitochondrial dysfunction, synaptic loss and cognitive impairment in young wild-type, but not Tau knockout, mice. In young IL-6 knockout mice, sevoflurane increased Tau phosphorylation but did not cause mitochondrial dysfunction, synaptic loss or cognitive impairment. Finally, sevoflurane increased Tau phosphorylation and IL-6 amount, but did not induce synaptic loss and cognitive impairment, in young CypD knockout mice or WT mice pretreated with idebenone, an analog of co-enzyme Q10. In conclusion, sevoflurane increased Tau phosphorylation, which caused IL-6 elevation, leading to mitochondrial dysfunction in young mice. Such interactions caused synaptic loss and cognitive impairment in the mice. Idebenone mitigated sevoflurane-induced cognitive impairment in young mice. These studies would promote more research to study Tau in young mice.

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