Galectin-1 ameliorates perioperative neurocognitive disorders in aged mice

Abstract Background The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation-mediated neuroinflammation is one of the hallmarks of PND. Galectin-1 has been identified as pivotal modulator in central nervous system (CNS), while the role of galectin-1 in PND induced by microglia-mediated neuroinflammation is still undetermined. Methods An exploratory laparotomy model anesthetized with isoflurane was employed to investigate the role of galectin-1 on PND in aged mice. Open field test and Morris water maze were used to test the cognitive function 3 or 7 days after surgery. Immunofluorescence staining was employed to detect the activation of microglia and neuronal integrity in the hippocampus of aged mice. Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to elucidate the underlying mechanisms. Results Pretreatment with galectin-1 attenuated the cognitive dysfunction induced by surgery in aged mice and inhibited microglial activity. Moreover, galectin-1 decreased the expression level of inflammatory proteins (interleukin-1β, interleukin-6 and tumor necrosis factor-α), and disrupted neuronal integrity in hippocampus. Galectin-1 inhibited the inflammation of BV2 microglial cells induced by lipopolysaccharide via decreasing the translocation of c-Jun and NF-κB p65, while this kind of inhibition was rescued when overexpressing IRAK1. Conclusions Our findings provide evidence that galectin-1 may inhibit IRAK1 expression, thus suppressing inflammatory response, inhibiting neuroinflammation, and improving ensuing cognitive dysfunction. Collectively, these findings unveil that galectin-1 may elicit protective effect on surgery-induced neuroinflammation and neurocognitive disorders.