Abnormal phosphorylation of tau protein and neuroinflammation induced by laparotomy in an animal model of postoperative delirium.

Abstract

Postoperative delirium (POD) is an acute neuropsychological disturbance after surgery, whoseprevalenceis related with advancing age. Neuroinflammation and abnormal tau phosphorylation that commonly presenting in Alzheimer's disease (AD) may contribute to the progression and duration of POD. To study the acute influence of surgery on cognitive function, wild type male C57BL/6N mice were randomly divided into three groups: Control (CON), Laparotomy at 4h and 24h (LAP-4h, LAP-24h), then subjected to laparotomy under sevoflurane anaesthesia. The cognitive performance, peripheral and central inflammatory responses and tau phosphorylation levels were evaluated at 4h and 24h postoperatively. When LAP4-hrs displayed anxiety behaviors with high mRNA levels of inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, IL-8, TNF-α and MCP-1 in the liver, and IL-8 in the hippocampus, results at 24h were different. In the liver, only IL-10 protein was obviously elevated, but in the hippocampus, both pro- and anti-inflammatory cytokines were significantly decreased whilst the elimination of anxiety. The activity of major related kinases and phosphatases was remarkably changed which may contribute to the dephosphorylated tau protein. With tremendous neuropathological changes and significant numbers of activated microglias and astrocytes observed in the sub-regions of hippocampus, the memory impairment existed at both 4h and 24h. Since the association of dephosphorylated tau with POD, these findings may supply novel implications for the understanding of tauopathies and as a theoretical basis for preventions from the postoperative cognitive dysfunction (POCD).