Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway
Abstract Recent studies have shown that abnormal activity of acid sphingomyelinase (Asm) has been associated with a range of psychiatric disorders including schizophrenia and depression. However, the role of Asm in the regulation of anxiety remains unclear. In the present study, we employed Asm-knoc...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-025-01178-x |
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| author | Huiqi Yuan Yanan Xu Hailun Jiang Meizhu Jiang Luofei Zhang Shifeng Wei Cao Li Zhigang Zhao |
| author_facet | Huiqi Yuan Yanan Xu Hailun Jiang Meizhu Jiang Luofei Zhang Shifeng Wei Cao Li Zhigang Zhao |
| author_sort | Huiqi Yuan |
| collection | DOAJ |
| description | Abstract Recent studies have shown that abnormal activity of acid sphingomyelinase (Asm) has been associated with a range of psychiatric disorders including schizophrenia and depression. However, the role of Asm in the regulation of anxiety remains unclear. In the present study, we employed Asm-knockout (Asm KO) mice to investigate the association between Asm and anxiety using behavioral tests, RNA sequencing, q-PCR, immunohistochemical staining, and other methods. The behavioral results showed that Asm KO mice exhibit enhanced anxiety-like behaviors, such as restricted activity, reduced cumulative times in the central area, diminished exploratory interest, delayed latency to feed, through behavioral tests including open field, novelty-suppressed feeding test, elevated plus maze test, ect. Transcriptional profiling combined with bioinformatics analysis revealed the upregulation of Toll-like receptor signaling pathway related gene including Tlr1/2, Ccl3, Ccl4, Ccl5 and Cd86 in Asm KO mice, which was further confirmed by the detection of activated microglia and astrocytes through iba-1 and GFAP immunohistochemical staining. Collectively, our findings uncover a role for Asm in regulating anxiety-like behavior and suggest that it may be essential for the maintenance of emotional stability, indicating its potential as a promising target for treating anxiety disorders. |
| format | Article |
| id | doaj-art-ae7679b087374f15a1873fee1ee1696a |
| institution | Kabale University |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj-art-ae7679b087374f15a1873fee1ee1696a2025-02-09T13:00:15ZengBMCMolecular Brain1756-66062025-02-0118111510.1186/s13041-025-01178-xAcid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathwayHuiqi Yuan0Yanan Xu1Hailun Jiang2Meizhu Jiang3Luofei Zhang4Shifeng Wei5Cao Li6Zhigang Zhao7Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Medicinal Chemistry, College of Pharmaceutical Sciences, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Recent studies have shown that abnormal activity of acid sphingomyelinase (Asm) has been associated with a range of psychiatric disorders including schizophrenia and depression. However, the role of Asm in the regulation of anxiety remains unclear. In the present study, we employed Asm-knockout (Asm KO) mice to investigate the association between Asm and anxiety using behavioral tests, RNA sequencing, q-PCR, immunohistochemical staining, and other methods. The behavioral results showed that Asm KO mice exhibit enhanced anxiety-like behaviors, such as restricted activity, reduced cumulative times in the central area, diminished exploratory interest, delayed latency to feed, through behavioral tests including open field, novelty-suppressed feeding test, elevated plus maze test, ect. Transcriptional profiling combined with bioinformatics analysis revealed the upregulation of Toll-like receptor signaling pathway related gene including Tlr1/2, Ccl3, Ccl4, Ccl5 and Cd86 in Asm KO mice, which was further confirmed by the detection of activated microglia and astrocytes through iba-1 and GFAP immunohistochemical staining. Collectively, our findings uncover a role for Asm in regulating anxiety-like behavior and suggest that it may be essential for the maintenance of emotional stability, indicating its potential as a promising target for treating anxiety disorders.https://doi.org/10.1186/s13041-025-01178-xAcid sphingomyelinaseAnxietyNeuroinflammationToll-like receptor signaling pathway |
| spellingShingle | Huiqi Yuan Yanan Xu Hailun Jiang Meizhu Jiang Luofei Zhang Shifeng Wei Cao Li Zhigang Zhao Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway Molecular Brain Acid sphingomyelinase Anxiety Neuroinflammation Toll-like receptor signaling pathway |
| title | Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway |
| title_full | Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway |
| title_fullStr | Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway |
| title_full_unstemmed | Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway |
| title_short | Acid sphingomyelinase modulates anxiety-like behavior likely through toll-like receptor signaling pathway |
| title_sort | acid sphingomyelinase modulates anxiety like behavior likely through toll like receptor signaling pathway |
| topic | Acid sphingomyelinase Anxiety Neuroinflammation Toll-like receptor signaling pathway |
| url | https://doi.org/10.1186/s13041-025-01178-x |
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