Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice

Journal of Neuroinflammation

Research

Xiaobin Sun¹  Qidi Zhang¹  Mengyuan Zhang²  Xiaowei Li²  Gongming Wang²  Hong Wang³ 

[1] Department of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China;Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, 250021, Jinan, Shandong, China;Department of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, 250021, Jinan, Shandong, China;Department of Nephrology, Tai’ an Central Hospital, 271000, Taian, Shandong, China;

关键词: Postoperative cognitive decline;    Adult hippocampal neurogenesis;    T-cell infiltration;    IFN-γ;    IFNGR1;   

DOI  :  10.1186/s12974-023-02910-x

 received in 2023-06-22, accepted in 2023-09-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSome patients show persistent cognitive decline for weeks, months or even years after surgery, which seriously affects their long-term prognosis and quality of life. However, most previous basic studies have focused mainly on the mechanisms of early postoperative cognitive decline, whereas cognitive decline in the longer term after surgery is less well-understood. The subgranular zone of the dentate gyrus exhibits life-long neurogenesis, supporting hippocampus-dependent learning and memory.Main textThe aim of this study was to investigate whether adult hippocampal neurogenesis (AHN) involves in cognitive decline later following surgery and to further explore the roles of CD8 + T lymphocytes infiltrating the hippocampal parenchyma after surgery in this pathological process. Cognitive function was examined in adult mice that underwent laparotomy combined with partial hepatectomy, and the results showed that cognitive decline persisted in mice who underwent surgery during the first postoperative month, even though there was a trend toward continuous improvement over time. Significantly decreased numbers of DCX + cells, BrdU + cells, and BrdU + /DCX + cells were observed on day 8 after surgery, and a significantly decreased number of NeuN + /BrdU + cells was observed on day 28 after surgery, which indicated inhibition of AHN. After surgery, T lymphocytes, the majority of which were CD8 + T cells, infiltrated the hippocampus and secreted Interferon-γ (IFN-γ). Depletion of CD8 + T cells could inhibit the increase of IFN-γ synthesis, improve hippocampal neurogenesis, and improve postoperative cognitive function. Hippocampal microinjection of IFN-γ neutralizing antibody or adeno-associated virus to knock down IFN-γ receptor 1 (IFNGR1) could also partially attenuate the inhibition of AHN and improve postoperative cognitive function.ConclusionsThese results demonstrate that postoperative infiltration of CD8 + T cells into the hippocampus and subsequent secretion of IFN-γ contribute to the inhibition of AHN and cognitive decline later following surgery.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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