Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS)
Delayed neurologic sequelae (DNS) are recurrent–transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-08-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00815/full |
| _version_ | 1818881392332767232 |
|---|---|
| author | Xiaofei Tian Xiaofei Tian Teng Guan Ying Guo Ying Guo Guohui Zhang Jiming Kong Jiming Kong |
| author_facet | Xiaofei Tian Xiaofei Tian Teng Guan Ying Guo Ying Guo Guohui Zhang Jiming Kong Jiming Kong |
| author_sort | Xiaofei Tian |
| collection | DOAJ |
| description | Delayed neurologic sequelae (DNS) are recurrent–transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of DNS. In an in vitro model of CO poisoning with the carbon monoxide releasing molecule-2 (CORM-2) as a CO donor, we show that CORM-2 at concentrations higher than 200 µM significantly inhibited viability and caused significant death of PC12 cells. Similar minimum toxicity concentration was observed on primary brain cells including neurons, astrocytes, and microglia. Interestingly, oligodendrocytes showed cytotoxicity to CORM-2 at a much lower concentration (100 µM). We further found that CORM-2 at 100 µM inhibited proteolipid protein (PLP) production and reduced myelin coverage on axons in an in vitro model of myelination. Our results show that direct cytotoxicity is a mechanism of CO poisoning and DNS may result from a high susceptibility of oligodendrocytes to CO poisoning. |
| first_indexed | 2024-12-19T15:01:08Z |
| format | Article |
| id | doaj.art-5bf3f2c68ecc4020ab4283f1bcfb20ad |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-19T15:01:08Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-5bf3f2c68ecc4020ab4283f1bcfb20ad2022-12-21T20:16:34ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-08-011110.3389/fpsyt.2020.00815525098Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS)Xiaofei Tian0Xiaofei Tian1Teng Guan2Ying Guo3Ying Guo4Guohui Zhang5Jiming Kong6Jiming Kong7Department of Forensic Medicine, Hebei North University, Zhangjiakou, ChinaDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, CanadaDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, CanadaDepartment of Forensic Medicine, Hebei North University, Zhangjiakou, ChinaDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, CanadaDepartment of Forensic Medicine, Hebei North University, Zhangjiakou, ChinaDepartment of Forensic Medicine, Hebei North University, Zhangjiakou, ChinaDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, CanadaDelayed neurologic sequelae (DNS) are recurrent–transient neuropsychiatric consequences of carbon monoxide (CO) intoxication. Pathologically DNS features damages to the brain white matter. Here we test a hypothesis that direct cytotoxicity of CO to oligodendrocytes plays a role in the development of DNS. In an in vitro model of CO poisoning with the carbon monoxide releasing molecule-2 (CORM-2) as a CO donor, we show that CORM-2 at concentrations higher than 200 µM significantly inhibited viability and caused significant death of PC12 cells. Similar minimum toxicity concentration was observed on primary brain cells including neurons, astrocytes, and microglia. Interestingly, oligodendrocytes showed cytotoxicity to CORM-2 at a much lower concentration (100 µM). We further found that CORM-2 at 100 µM inhibited proteolipid protein (PLP) production and reduced myelin coverage on axons in an in vitro model of myelination. Our results show that direct cytotoxicity is a mechanism of CO poisoning and DNS may result from a high susceptibility of oligodendrocytes to CO poisoning.https://www.frontiersin.org/article/10.3389/fpsyt.2020.00815/fullcarbon monoxidecytotoxicityoligodendrocytedemyelinationdelayed neurologic sequelae |
| spellingShingle | Xiaofei Tian Xiaofei Tian Teng Guan Ying Guo Ying Guo Guohui Zhang Jiming Kong Jiming Kong Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) Frontiers in Psychiatry carbon monoxide cytotoxicity oligodendrocyte demyelination delayed neurologic sequelae |
| title | Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) |
| title_full | Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) |
| title_fullStr | Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) |
| title_full_unstemmed | Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) |
| title_short | Selective Susceptibility of Oligodendrocytes to Carbon Monoxide Poisoning: Implication for Delayed Neurologic Sequelae (DNS) |
| title_sort | selective susceptibility of oligodendrocytes to carbon monoxide poisoning implication for delayed neurologic sequelae dns |
| topic | carbon monoxide cytotoxicity oligodendrocyte demyelination delayed neurologic sequelae |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2020.00815/full |
| work_keys_str_mv | AT xiaofeitian selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT xiaofeitian selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT tengguan selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT yingguo selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT yingguo selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT guohuizhang selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT jimingkong selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns AT jimingkong selectivesusceptibilityofoligodendrocytestocarbonmonoxidepoisoningimplicationfordelayedneurologicsequelaedns |