G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation
Chronic stress is thought to be a major contributor to the onset of mental disorders such as anxiety disorders. Several studies have demonstrated a correlation between anxiety state and neuroinflammation, but the detailed mechanism is unclear. Chitinase-3-like 1 (CHI3L1) is expressed in several chro...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.793835/full |
| _version_ | 1818918789464457216 |
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| author | Hyeon Joo Ham Yong Sun Lee Hee Pom Lee Young Wan Ham Jaesuk Yun Sang Bae Han Jin Tae Hong |
| author_facet | Hyeon Joo Ham Yong Sun Lee Hee Pom Lee Young Wan Ham Jaesuk Yun Sang Bae Han Jin Tae Hong |
| author_sort | Hyeon Joo Ham |
| collection | DOAJ |
| description | Chronic stress is thought to be a major contributor to the onset of mental disorders such as anxiety disorders. Several studies have demonstrated a correlation between anxiety state and neuroinflammation, but the detailed mechanism is unclear. Chitinase-3-like 1 (CHI3L1) is expressed in several chronic inflammatorily damaged tissues and is well known to play a major role in mediating inflammatory responses. In the present study, we investigated the anxiolytic-like effect of N-Allyl-2-[(6-butyl-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)sulfanyl]acetamide (G721-0282), an inhibitor of CHI3L1, on mice treated with chronic unpredictable mild stress (CUMS), as well as the mechanism of its action. We examined the anxiolytic-like effect of G721-0282 by conducting several behavioral tests with oral administration of G721-0282 to CUMS-treated BALB/c male mice. We found that administration of G721-0282 relieves CUMS-induced anxiety. Anxiolytic-like effects of G721-0282 have been shown to be associated with decreased expressions of CUMS-induced inflammatory proteins and cytokines in the hippocampus. The CUMS-elevated levels of CHI3L1 and IGFBP3 were inhibited by treatment with G721-0282 in vivo and in vitro. However, CHI3L1 deficiency abolished the anti-inflammatory effects of G721-0282 in microglial BV-2 cells. These results suggest that G721-0282 could lower CUMS-induced anxiety like behaviors by regulating IGFBP3-mediated neuroinflammation via inhibition of CHI3L1. |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-20T00:55:33Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-506c7e62bbcc4b29858eb10219e696f02022-12-21T19:59:08ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-03-011610.3389/fncel.2022.793835793835G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated NeuroinflammationHyeon Joo Ham0Yong Sun Lee1Hee Pom Lee2Young Wan Ham3Jaesuk Yun4Sang Bae Han5Jin Tae Hong6College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaCollege of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaCollege of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaDepartment of Chemistry, Utah Valley University, Orem, UT, United StatesCollege of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaCollege of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaCollege of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, South KoreaChronic stress is thought to be a major contributor to the onset of mental disorders such as anxiety disorders. Several studies have demonstrated a correlation between anxiety state and neuroinflammation, but the detailed mechanism is unclear. Chitinase-3-like 1 (CHI3L1) is expressed in several chronic inflammatorily damaged tissues and is well known to play a major role in mediating inflammatory responses. In the present study, we investigated the anxiolytic-like effect of N-Allyl-2-[(6-butyl-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)sulfanyl]acetamide (G721-0282), an inhibitor of CHI3L1, on mice treated with chronic unpredictable mild stress (CUMS), as well as the mechanism of its action. We examined the anxiolytic-like effect of G721-0282 by conducting several behavioral tests with oral administration of G721-0282 to CUMS-treated BALB/c male mice. We found that administration of G721-0282 relieves CUMS-induced anxiety. Anxiolytic-like effects of G721-0282 have been shown to be associated with decreased expressions of CUMS-induced inflammatory proteins and cytokines in the hippocampus. The CUMS-elevated levels of CHI3L1 and IGFBP3 were inhibited by treatment with G721-0282 in vivo and in vitro. However, CHI3L1 deficiency abolished the anti-inflammatory effects of G721-0282 in microglial BV-2 cells. These results suggest that G721-0282 could lower CUMS-induced anxiety like behaviors by regulating IGFBP3-mediated neuroinflammation via inhibition of CHI3L1.https://www.frontiersin.org/articles/10.3389/fncel.2022.793835/fullchronic unpredictabe mild stressneuroinflammationchitinase-3-like 1IGFBP3microglia activation |
| spellingShingle | Hyeon Joo Ham Yong Sun Lee Hee Pom Lee Young Wan Ham Jaesuk Yun Sang Bae Han Jin Tae Hong G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation Frontiers in Cellular Neuroscience chronic unpredictabe mild stress neuroinflammation chitinase-3-like 1 IGFBP3 microglia activation |
| title | G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation |
| title_full | G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation |
| title_fullStr | G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation |
| title_full_unstemmed | G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation |
| title_short | G721-0282 Exerts Anxiolytic-Like Effects on Chronic Unpredictable Mild Stress in Mice Through Inhibition of Chitinase-3-Like 1-Mediated Neuroinflammation |
| title_sort | g721 0282 exerts anxiolytic like effects on chronic unpredictable mild stress in mice through inhibition of chitinase 3 like 1 mediated neuroinflammation |
| topic | chronic unpredictabe mild stress neuroinflammation chitinase-3-like 1 IGFBP3 microglia activation |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.793835/full |
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