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...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-10-01
|
| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025003090 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 1873-2747 |