Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway
Sevoflurane is a widely used anesthetic in elderly patients and has been linked to postoperative cognitive dysfunction; however, its molecular mechanisms remain unclear. Inhibition of adult hippocampal neurogenesis (AHN) and epigenetic alterations, particularly via histone deacetylase 8 (HDAC8), hav...
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Elsevier
2025-10-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025003090 |
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| author | Yingxue He Yanjing Guo Xiaowei Li Jiangnan Wu Zunsai Feng Gongming Wang Mengyuan Zhang |
| author_facet | Yingxue He Yanjing Guo Xiaowei Li Jiangnan Wu Zunsai Feng Gongming Wang Mengyuan Zhang |
| author_sort | Yingxue He |
| collection | DOAJ |
| description | Sevoflurane is a widely used anesthetic in elderly patients and has been linked to postoperative cognitive dysfunction; however, its molecular mechanisms remain unclear. Inhibition of adult hippocampal neurogenesis (AHN) and epigenetic alterations, particularly via histone deacetylase 8 (HDAC8), have emerged as potential contributors to these deficits. Using young and aged C57BL/6 J male mice exposed to varying sevoflurane concentrations, we evaluated cognitive function and AHN. High-concentration (3 %) sevoflurane impaired both cognition and AHN in aged mice, correlating with reduced histone acetylation, increased HDAC8 expression, and diminished pCREB/BDNF signaling. Notably, HDAC8 inhibition with PCI-34051 or direct BDNF administration reversed these effects, while HDAC8 overexpression recapitulated the deficits. These findings suggest that HDAC8 upregulation is a key mediator of sevoflurane-induced cognitive decline via AHN suppression, highlighting a promising therapeutic target for anesthesia-related neurotoxicity. |
| format | Article |
| id | doaj-art-7bf2163cfec741a6bf8613cb0d91a4d2 |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-7bf2163cfec741a6bf8613cb0d91a4d22025-08-20T03:36:37ZengElsevierBrain Research Bulletin1873-27472025-10-0123011149710.1016/j.brainresbull.2025.111497Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathwayYingxue He0Yanjing Guo1Xiaowei Li2Jiangnan Wu3Zunsai Feng4Gongming Wang5Mengyuan Zhang6Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Corresponding authors at: Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaDepartment of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Corresponding authors at: Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, ChinaSevoflurane is a widely used anesthetic in elderly patients and has been linked to postoperative cognitive dysfunction; however, its molecular mechanisms remain unclear. Inhibition of adult hippocampal neurogenesis (AHN) and epigenetic alterations, particularly via histone deacetylase 8 (HDAC8), have emerged as potential contributors to these deficits. Using young and aged C57BL/6 J male mice exposed to varying sevoflurane concentrations, we evaluated cognitive function and AHN. High-concentration (3 %) sevoflurane impaired both cognition and AHN in aged mice, correlating with reduced histone acetylation, increased HDAC8 expression, and diminished pCREB/BDNF signaling. Notably, HDAC8 inhibition with PCI-34051 or direct BDNF administration reversed these effects, while HDAC8 overexpression recapitulated the deficits. These findings suggest that HDAC8 upregulation is a key mediator of sevoflurane-induced cognitive decline via AHN suppression, highlighting a promising therapeutic target for anesthesia-related neurotoxicity.http://www.sciencedirect.com/science/article/pii/S0361923025003090SevofluraneAdult hippocampal neurogenesisHistone acetylationCognitive dysfunction |
| spellingShingle | Yingxue He Yanjing Guo Xiaowei Li Jiangnan Wu Zunsai Feng Gongming Wang Mengyuan Zhang Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway Brain Research Bulletin Sevoflurane Adult hippocampal neurogenesis Histone acetylation Cognitive dysfunction |
| title | Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway |
| title_full | Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway |
| title_fullStr | Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway |
| title_full_unstemmed | Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway |
| title_short | Sevoflurane-induced cognitive dysfunction in aged mice mediated by HDAC8-dependent suppression of adult hippocampal neurogenesis via the pCREB/BDNF pathway |
| title_sort | sevoflurane induced cognitive dysfunction in aged mice mediated by hdac8 dependent suppression of adult hippocampal neurogenesis via the pcreb bdnf pathway |
| topic | Sevoflurane Adult hippocampal neurogenesis Histone acetylation Cognitive dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025003090 |
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