Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice
Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Its neuropathogenesis has not been clearly identified and effective interventions for clinical use to reduce POCD have not been established. This study was designed to determine whether environmental enrichment (EE) or cogni...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/727 |
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| author | Lingli Gui Zhen Luo Weiran Shan Zhiyi Zuo |
| author_facet | Lingli Gui Zhen Luo Weiran Shan Zhiyi Zuo |
| author_sort | Lingli Gui |
| collection | DOAJ |
| description | Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Its neuropathogenesis has not been clearly identified and effective interventions for clinical use to reduce POCD have not been established. This study was designed to determine whether environmental enrichment (EE) or cognitive enrichment (CE) reduces POCD and whether sex-determining region Y-box-2 regulated by sirtuin 1, plays a role in the effect. Eighteen-month-old male mice were subjected to right-common-carotid-artery exposure under sevoflurane anesthesia. Some of them stayed in cages with EE or CE after the surgery. Learning and memory of mice were tested by a Barnes maze and fear conditioning, starting 2 weeks after the surgery. Sex-determining region Y-box-2 (Sox2) in the brain was silenced by small hairpin RNA (shRNA). Immunofluorescent staining was used to quantify Sox2-positive cells. Surgery reduced Sox2-positive cells in the hippocampus (64 ± 9 cells vs. 91 ± 9 cells in control group, <i>n</i> = 6, <i>p</i> < 0.001) and impaired learning and memory (time to identify target box one day after training sessions in the Barnes maze test: 132 ± 53 s vs. 79 ± 53 s in control group, <i>n</i> = 10, <i>p</i> = 0.040). EE or CE applied after surgery attenuated this reduction of Sox2 cells and POCD. Surgery reduced sirtuin 1 activity and CE attenuated this reduction. Resveratrol, a sirtuin 1 activator, attenuated POCD and surgery-induced decrease of Sox2-positive cells. Silencing shRNA reduced the Sox2-positive cells in the hippocampus and impaired learning and memory in mice without surgery. These results suggest a role of Sox2 in learning, memory, and POCD. EE and CE attenuated POCD via maintaining Sox2-positive cells in the hippocampus. |
| first_indexed | 2024-03-10T12:56:37Z |
| format | Article |
| id | doaj.art-e52694e78c0344fa92225dce9fb48b87 |
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| language | English |
| last_indexed | 2024-03-10T12:56:37Z |
| publishDate | 2021-03-01 |
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| series | Cells |
| spelling | doaj.art-e52694e78c0344fa92225dce9fb48b872023-11-21T11:54:11ZengMDPI AGCells2073-44092021-03-0110472710.3390/cells10040727Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in MiceLingli Gui0Zhen Luo1Weiran Shan2Zhiyi Zuo3Department of Anesthesiology, University of Virginia, Charlottesville, VA 22901, USADepartment of Anesthesiology, University of Virginia, Charlottesville, VA 22901, USADepartment of Anesthesiology, University of Virginia, Charlottesville, VA 22901, USADepartment of Anesthesiology, University of Virginia, Charlottesville, VA 22901, USAPostoperative cognitive dysfunction (POCD) is a significant clinical issue. Its neuropathogenesis has not been clearly identified and effective interventions for clinical use to reduce POCD have not been established. This study was designed to determine whether environmental enrichment (EE) or cognitive enrichment (CE) reduces POCD and whether sex-determining region Y-box-2 regulated by sirtuin 1, plays a role in the effect. Eighteen-month-old male mice were subjected to right-common-carotid-artery exposure under sevoflurane anesthesia. Some of them stayed in cages with EE or CE after the surgery. Learning and memory of mice were tested by a Barnes maze and fear conditioning, starting 2 weeks after the surgery. Sex-determining region Y-box-2 (Sox2) in the brain was silenced by small hairpin RNA (shRNA). Immunofluorescent staining was used to quantify Sox2-positive cells. Surgery reduced Sox2-positive cells in the hippocampus (64 ± 9 cells vs. 91 ± 9 cells in control group, <i>n</i> = 6, <i>p</i> < 0.001) and impaired learning and memory (time to identify target box one day after training sessions in the Barnes maze test: 132 ± 53 s vs. 79 ± 53 s in control group, <i>n</i> = 10, <i>p</i> = 0.040). EE or CE applied after surgery attenuated this reduction of Sox2 cells and POCD. Surgery reduced sirtuin 1 activity and CE attenuated this reduction. Resveratrol, a sirtuin 1 activator, attenuated POCD and surgery-induced decrease of Sox2-positive cells. Silencing shRNA reduced the Sox2-positive cells in the hippocampus and impaired learning and memory in mice without surgery. These results suggest a role of Sox2 in learning, memory, and POCD. EE and CE attenuated POCD via maintaining Sox2-positive cells in the hippocampus.https://www.mdpi.com/2073-4409/10/4/727cognitive enrichmentenvironmental enrichmentmicepostoperative cognitive dysfunctionsex-determining region Y-box-2 |
| spellingShingle | Lingli Gui Zhen Luo Weiran Shan Zhiyi Zuo Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice Cells cognitive enrichment environmental enrichment mice postoperative cognitive dysfunction sex-determining region Y-box-2 |
| title | Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice |
| title_full | Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice |
| title_fullStr | Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice |
| title_full_unstemmed | Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice |
| title_short | Role of Sox2 in Learning, Memory, and Postoperative Cognitive Dysfunction in Mice |
| title_sort | role of sox2 in learning memory and postoperative cognitive dysfunction in mice |
| topic | cognitive enrichment environmental enrichment mice postoperative cognitive dysfunction sex-determining region Y-box-2 |
| url | https://www.mdpi.com/2073-4409/10/4/727 |
| work_keys_str_mv | AT lingligui roleofsox2inlearningmemoryandpostoperativecognitivedysfunctioninmice AT zhenluo roleofsox2inlearningmemoryandpostoperativecognitivedysfunctioninmice AT weiranshan roleofsox2inlearningmemoryandpostoperativecognitivedysfunctioninmice AT zhiyizuo roleofsox2inlearningmemoryandpostoperativecognitivedysfunctioninmice |