The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis
Abstract Background Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice. Methods...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-024-01057-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850118773004042240 |
|---|---|
| author | Fangwei Zhou Yiting Jiang Yangsong Li Jianyao Li Tian Zhang Guodong Yu |
| author_facet | Fangwei Zhou Yiting Jiang Yangsong Li Jianyao Li Tian Zhang Guodong Yu |
| author_sort | Fangwei Zhou |
| collection | DOAJ |
| description | Abstract Background Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice. Methods A CRS mouse model was developed, and behavioral assessments were conducted to evaluate anxiety and depression-like behaviors. Techniques including 18F-FDG PET, Nissl staining, and immunofluorescence were used to assess hippocampal metabolic activity in CRS mice. Western Blot and RT-qPCR were employed to measure HMGB1 and Notch1/Hes-1 expression in the hippocampus, while ELISA determined inflammatory cytokine levels. The study also examined the effects of metformin on these behaviors and its mechanisms. Results CRS mice exhibited increased anxiety and depression-like behaviors, accompanied by enhanced hippocampal metabolic activity. HMGB1-siRNA treatment reduced these behaviors. Hippocampal glucose metabolism was markedly higher in CRS mice than in controls. Nissl staining revealed hippocampal neuron damage, and immunofluorescence indicated microglial activation in CRS mice. Reducing HMGB1 expression inhibited Notch1/Hes-1 pathway activation. In microglia, HMGB1 knockdown suppressed the Notch1/Hes-1 pathway, reducing inflammatory cytokine secretion. Metformin improved neuropsychiatric symptoms in CRS mice by inhibiting the Notch1/Hes-1 pathway after HMGB1 downregulation. Conclusion HMGB1 activates the microglial Notch1/Hes-1 pathway in CRS mice, promoting neuroinflammation and anxiety and depression-like behaviors. Metformin alleviates these effects. |
| format | Article |
| id | doaj-art-cedce279eef546d6a5178dce09e76f19 |
| institution | OA Journals |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-cedce279eef546d6a5178dce09e76f192025-08-20T02:35:47ZengBMCMolecular Medicine1528-36582025-01-0131111910.1186/s10020-024-01057-6The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitisFangwei Zhou0Yiting Jiang1Yangsong Li2Jianyao Li3Tian Zhang4Guodong Yu5Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityDepartment of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical UniversityAbstract Background Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice. Methods A CRS mouse model was developed, and behavioral assessments were conducted to evaluate anxiety and depression-like behaviors. Techniques including 18F-FDG PET, Nissl staining, and immunofluorescence were used to assess hippocampal metabolic activity in CRS mice. Western Blot and RT-qPCR were employed to measure HMGB1 and Notch1/Hes-1 expression in the hippocampus, while ELISA determined inflammatory cytokine levels. The study also examined the effects of metformin on these behaviors and its mechanisms. Results CRS mice exhibited increased anxiety and depression-like behaviors, accompanied by enhanced hippocampal metabolic activity. HMGB1-siRNA treatment reduced these behaviors. Hippocampal glucose metabolism was markedly higher in CRS mice than in controls. Nissl staining revealed hippocampal neuron damage, and immunofluorescence indicated microglial activation in CRS mice. Reducing HMGB1 expression inhibited Notch1/Hes-1 pathway activation. In microglia, HMGB1 knockdown suppressed the Notch1/Hes-1 pathway, reducing inflammatory cytokine secretion. Metformin improved neuropsychiatric symptoms in CRS mice by inhibiting the Notch1/Hes-1 pathway after HMGB1 downregulation. Conclusion HMGB1 activates the microglial Notch1/Hes-1 pathway in CRS mice, promoting neuroinflammation and anxiety and depression-like behaviors. Metformin alleviates these effects.https://doi.org/10.1186/s10020-024-01057-6Chronic rhinosinusitisAnxiety and depression-like behaviorsHMGB1MicrogliaMetformin |
| spellingShingle | Fangwei Zhou Yiting Jiang Yangsong Li Jianyao Li Tian Zhang Guodong Yu The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis Molecular Medicine Chronic rhinosinusitis Anxiety and depression-like behaviors HMGB1 Microglia Metformin |
| title | The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis |
| title_full | The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis |
| title_fullStr | The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis |
| title_full_unstemmed | The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis |
| title_short | The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis |
| title_sort | role and mechanism of hmgb1 mediated notch1 hes 1 pathway in anxiety and depression like behaviors in mice with chronic rhinosinusitis |
| topic | Chronic rhinosinusitis Anxiety and depression-like behaviors HMGB1 Microglia Metformin |
| url | https://doi.org/10.1186/s10020-024-01057-6 |
| work_keys_str_mv | AT fangweizhou theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT yitingjiang theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT yangsongli theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT jianyaoli theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT tianzhang theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT guodongyu theroleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT fangweizhou roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT yitingjiang roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT yangsongli roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT jianyaoli roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT tianzhang roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis AT guodongyu roleandmechanismofhmgb1mediatednotch1hes1pathwayinanxietyanddepressionlikebehaviorsinmicewithchronicrhinosinusitis |