Abstract
BackgroundPerioperative neurocognitive disorders (PNDs) are common complications of surgical patients, which can lead to prolonged hospitalization, increased complications, and decreased independence and quality of life. However, the underlying molecular mechanisms of PND remain largely obscure. Microglia activation and synapse loss were observed in PND. Cluster of differentiation 47 (CD47), which can bind to its receptor signal regulatory protein alpha (SIRPα) and generate “do not eat me” signal, protects synapses from excessive pruning. Therefore, we aimed to evaluate the potential role of CD47–SIRPα signaling in PND.MethodsThe tibial fracture surgery was performed in aged C57BL/6 mice for PND model establishment. The expression of CD47 and SIRPα in the hippocampus was assessed. Synaptic plasticity, dendritic spine density, microglial engulfment, and hippocampal-dependent memory function were evaluated after model establishment and intervention with SIRPα overexpression.ResultsCD47 and SIRPα expression in the hippocampus were both decreased after the surgery. SIRPα overexpression showed reduced engulfment within host microglia, but a total effect of excessive synapse engulfment decreased dendritic spine density and post-synaptic density protein 95 (PSD95) expression. SIRPα overexpression could not improve the synaptic dysfunction and cognitive impairment in PND. In addition, SIRPα overexpression led to increased CD47 and Iba1 expression.ConclusionAnesthesia and surgery affect CD47–SIRPα signaling. SIRPα overexpression could not ameliorate the cognitive impairment in PND mice. One reason may be that the increased Iba1 expression leads to a total effect of excessive synapse engulfment, which results in decreased dendritic spine density and PSD95 expression.
Highlights
Perioperative neurocognitive disorders (PNDs) are common complications of surgical patients, especially in elderly patients
We demonstrated that the protein expression of both Cluster of differentiation 47 (CD47) and SIRPα in the hippocampus was significantly reduced in mouse model of PND
We found that anesthesia and surgery induced spine loss of neurons in CA1 region and dentate gyrus (DG) of hippocampus
Summary
Perioperative neurocognitive disorders (PNDs) are common complications of surgical patients, especially in elderly patients. Microglia play a critical role in phagocytosis and synaptic pruning in the brain, but its activation can lead to harm (Lehrman et al, 2018; Pluvinage et al, 2019; Werneburg et al, 2020; Ding et al, 2021). Microglia can recognize the “eat me” and “do not eat me” signals to facilitate or suppress the phagocytosis (Lehrman et al, 2018; Rivest, 2018; Pluvinage et al, 2019; Miyanishi et al, 2021). Scientists have paid much attention to negative regulators of phagocytosis—the “do not eat me” signals (Lehrman et al, 2018; Pluvinage et al, 2019; Ding et al, 2021). Perioperative neurocognitive disorders (PNDs) are common complications of surgical patients, which can lead to prolonged hospitalization, increased complications, and decreased independence and quality of life. The underlying molecular mechanisms of PND remain largely obscure. We aimed to evaluate the potential role of CD47–SIRPα signaling in PND
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
