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Updated: Jul 8, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
The Role of Hippocampal Microglial cGAS-STING Signaling Pathway in Postoperative Cognitive Dysfunction in Diabetic
Jiaqi Ning1, Mengjie Chen1, Jiaxi Liu1
1Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 100010 Beijing, China.
Objective:
This study aimed to determine whether activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway within hippocampal microglia contributes to postoperative cognitive dysfunction (POCD) in a diabetic mouse model. Diabetes was induced using a high-fat, high-sugar (HFHS) diet combined with streptozotocin (STZ).
Methods:
Diabetes was induced in C57BL/6J mice using an HFHS diet followed by STZ. POCD was modeled via tibial fracture surgery under general anesthesia. Cognitive function was assessed using the Open Field Test, Y-maze, and contextual fear conditioning. cGAS-STING pathway activation was evaluated by western blot for cGAS and STING expression. Microglial activation was assessed by co-localization of Iba-1 and CD68 by immunofluorescence, and the co-localization of STING with Iba-1 in the hippocampus was examined by immunofluorescence. Hippocampal neuroinflammation was quantified by enzyme-linked immunosorbent assay (ELISA) for interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Neuronal injury and apoptosis were evaluated by Nissl staining and western blot for cleaved caspase-3.
Results:
Compared to non-diabetic controls, diabetic mice exhibited cognitive impairments, which were more pronounced in those that underwent surgery. This was accompanied by significant hippocampal neuronal loss, upregulated cleaved caspase-3 expression, and elevated IL-1β and TNF-α levels. Furthermore, diabetic mice that underwent surgery displayed increased expression of microglial activation markers (Iba-1 and CD68) and evidence of cGAS-STING pathway activation in the hippocampus. Immunofluorescence co-localization experiments further suggested a predominant association of this pathway with the microglial marker Iba-1.
Conclusion:
These findings suggest that surgery-associated overactivation of the microglial cGAS-STING pathway in the hippocampus may exacerbate neuroinflammation and neuronal injury, thereby contributing to cognitive decline in diabetic mice.
