Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects
Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Util...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:45210d806236489883266b9dfdf45b682021-11-18T07:56:30ZExogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects1663-981210.3389/fphar.2021.757417https://doaj.org/article/45210d806236489883266b9dfdf45b682021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.757417/fullhttps://doaj.org/toc/1663-9812Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.Yixiao LuoYixiao LuoRafi UllahJinfeng WangYuru DuShihao HuangLi MengYuan GaoYuan GaoMiao GongEwa GalajXi YinXi YinHaishui ShiHaishui ShiFrontiers Media S.A.articlecarbon monoxideheme oxygenase-1depressionanxietyinflammationTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
carbon monoxide heme oxygenase-1 depression anxiety inflammation Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
carbon monoxide heme oxygenase-1 depression anxiety inflammation Therapeutics. Pharmacology RM1-950 Yixiao Luo Yixiao Luo Rafi Ullah Jinfeng Wang Yuru Du Shihao Huang Li Meng Yuan Gao Yuan Gao Miao Gong Ewa Galaj Xi Yin Xi Yin Haishui Shi Haishui Shi Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| description |
Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety. |
| format |
article |
| author |
Yixiao Luo Yixiao Luo Rafi Ullah Jinfeng Wang Yuru Du Shihao Huang Li Meng Yuan Gao Yuan Gao Miao Gong Ewa Galaj Xi Yin Xi Yin Haishui Shi Haishui Shi |
| author_facet |
Yixiao Luo Yixiao Luo Rafi Ullah Jinfeng Wang Yuru Du Shihao Huang Li Meng Yuan Gao Yuan Gao Miao Gong Ewa Galaj Xi Yin Xi Yin Haishui Shi Haishui Shi |
| author_sort |
Yixiao Luo |
| title |
Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| title_short |
Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| title_full |
Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| title_fullStr |
Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| title_full_unstemmed |
Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects |
| title_sort |
exogenous carbon monoxide produces rapid antidepressant- and anxiolytic-like effects |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/45210d806236489883266b9dfdf45b68 |
| work_keys_str_mv |
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