Although
postoperative cognitive dysfunction (POCD) is relatively common in elderly patients who have undergone major surgery, the mechanisms underlying this postoperative complication are unclear. Previously, we have investigated the role of
cytokine-mediated hippocampal
inflammation in the development of POCD in a rat model. Here, we sought to determine in mice the role of
cytokine interleukin17A (IL17A) in POCD and to characterize the associated signaling pathways. Old mice underwent
hepatectomy surgery in the presence or absence of IL17A
monoclonal antibody, and cognitive function, hippocampal
neuroinflammation, and pathologic markers of
Alzheimer's disease (AD) were assessed. We found that the level of IL17A in the hippocampus was increased in
hepatectomy mice and that
cognitive impairment after surgery was associated with the appearance of certain pathological hallmarks of AD: activation of astrocytes, β-amyloid1-42 (Aβ1-42) production, upregulation of
transforming growth factor-β (TGFβ), and increased phosphorylation of signaling mother against decapentaplegic
peptide 3 (
Smad3) protein in the hippocampus. Surgery-induced changes in
cognitive dysfunction and changes in Aβ1-42 and TGFβ/Smad signaling were prevented by the administration of IL17A
monoclonal antibody. In addition, IL17A-stimulated TGFβ/Smad activation and Aβ1-42 expression were reversed by IL17A receptor
small interfering RNA and a TGFβ receptor inhibitor in cultured astrocytes. Our findings suggest that surgery can provoke IL17A-related hippocampal damage, as characterized by activation of astrocytes and TGFβ/Smad pathway dependent Aβ1-42 accumulation in old subjects. These changes likely contribute to the
cognitive decline seen in POCD.