【Abstract】 Objective To investigate whether Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is involved in perioperative neurocognitive disorders in adult mice. Methods Twenty male wildtype C57BL/6 mice were randomly divided into control group and operation group (n=10). Fear conditioning training was performed 24 hours before operation, and fear conditioning test (FCT) was performed on 1, 3 and 7 days after operation. Open field test was used to evaluate the motor ability of mice. After the last behavioral evaluation, the animals were killed and the expression of TREM2 was detected by Western blot. Forty mice were randomly divided into four groups (n=10): control group, operation group, heat shock protein 60 (Hsp60)+operation group and TREM2 siRNA+Hsp60+operation group. TREM2 siRNA was stereotaxically injected into the lateral ventricle 30 minutes before operation. HSP60, a selective TREM2 receptor agonist, was injected intraperitoneally for 5 minutes immediately after anesthesia μ The mice were given fear conditioning training 24 hours before operation, and FCT was performed 1, 3 and 7 days after operation respectively. The open field test was used to evaluate the motor ability of the mice. After the last behavioral evaluation, half of the mice (n=5) were used for Western blot and ELISA analysis, and the other half (n=5) were used for immunofluorescence detection. Results Intramedullary fixation of tibial fracture in adult C57BL/6 mice was performed under isoflurane anesthesia. It was found that the operation did not damage the movement ability of mice, but worsened the learning and memory function and decreased the expression of TREM2. Through the use of selective TREM2 agonist HSP60, we found that the expression of TREM2 in the hippocampus of mice was significantly increased, which improved learning and memory, and reduced the neuroinflammatory response of mice. However, TREM2 siRNA abolished the Hsp60 induced increase of TREM2 expression and reversed the Hsp60 induced improvement of learning and memory function and neuroinflammation in mice.Conclusion Upregulation of TREM2 may be associated with alleviated neuroinflammation and improved learning and memory function, and reducing the occurrence of PND.