Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice
Abstract Background Some 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 declin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02910-x |
| _version_ | 1797557641743958016 |
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| author | Xiaowei Li Hong Wang Qidi Zhang Xiaobin Sun Mengyuan Zhang Gongming Wang |
| author_facet | Xiaowei Li Hong Wang Qidi Zhang Xiaobin Sun Mengyuan Zhang Gongming Wang |
| author_sort | Xiaowei Li |
| collection | DOAJ |
| description | Abstract Background Some 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 text The 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. Conclusions These 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. |
| first_indexed | 2024-03-10T17:19:29Z |
| format | Article |
| id | doaj.art-a97241ea6ca641f592890290905ba110 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-03-10T17:19:29Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a97241ea6ca641f592890290905ba1102023-11-20T10:24:09ZengBMCJournal of Neuroinflammation1742-20942023-10-0120111910.1186/s12974-023-02910-xInhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult miceXiaowei Li0Hong Wang1Qidi Zhang2Xiaobin Sun3Mengyuan Zhang4Gongming Wang5Department of Anesthesiology, Shandong Provincial Hospital, Shandong UniversityDepartment of Nephrology, Tai’ an Central HospitalDepartment of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong First Medical UniversityDepartment of Anesthesiology, Shandong Provincial Hospital affiliated to Shandong First Medical UniversityDepartment of Anesthesiology, Shandong Provincial Hospital, Shandong UniversityDepartment of Anesthesiology, Shandong Provincial Hospital, Shandong UniversityAbstract Background Some 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 text The 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. Conclusions These 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.https://doi.org/10.1186/s12974-023-02910-xPostoperative cognitive declineAdult hippocampal neurogenesisT-cell infiltrationIFN-γIFNGR1 |
| spellingShingle | Xiaowei Li Hong Wang Qidi Zhang Xiaobin Sun Mengyuan Zhang Gongming Wang 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 Postoperative cognitive decline Adult hippocampal neurogenesis T-cell infiltration IFN-γ IFNGR1 |
| title | Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice |
| title_full | Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice |
| title_fullStr | Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice |
| title_full_unstemmed | Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice |
| title_short | Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice |
| title_sort | inhibition of adult hippocampal neurogenesis induced by postoperative cd8 t cell infiltration is associated with cognitive decline later following surgery in adult mice |
| topic | Postoperative cognitive decline Adult hippocampal neurogenesis T-cell infiltration IFN-γ IFNGR1 |
| url | https://doi.org/10.1186/s12974-023-02910-x |
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