Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice
The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/mi...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/337 |
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| author | Yi Ru Xianxie Zhang Baoying Shen Chunqi Yang Huijing Yu Zuoxu Liu Xiangjun Wu Fangyang Li Jialu Cui Chengcai Lai Yuguang Wang Yue Gao |
| author_facet | Yi Ru Xianxie Zhang Baoying Shen Chunqi Yang Huijing Yu Zuoxu Liu Xiangjun Wu Fangyang Li Jialu Cui Chengcai Lai Yuguang Wang Yue Gao |
| author_sort | Yi Ru |
| collection | DOAJ |
| description | The aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening. |
| first_indexed | 2024-03-08T15:04:55Z |
| format | Article |
| id | doaj.art-0140060c8ed2428ba20c2bb59319d5db |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:04:55Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0140060c8ed2428ba20c2bb59319d5db2024-01-10T14:59:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125133710.3390/ijms25010337Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J MiceYi Ru0Xianxie Zhang1Baoying Shen2Chunqi Yang3Huijing Yu4Zuoxu Liu5Xiangjun Wu6Fangyang Li7Jialu Cui8Chengcai Lai9Yuguang Wang10Yue Gao11Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaDepartment of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, ChinaThe aim of this study was to provide a suitable mouse model of radiation-induced delayed reaction and identify potential targets for drug development related to the prevention and treatment of radiation injury. C57BL/6J mice were subjected to singular (109 cGy/min, 5 Gy*1) and fractional (109 cGy/min, 5 Gy*2) total body irradiation. The behavior and activity of mice were assessed 60 days after ionizing radiation (IR) exposure. After that, the pathological changes and mechanism of the mouse brain and femoral tissues were observed by HE, Nissl, Trap staining micro-CT scanning and RNA sequencing (RNA-Seq), and Western blot. The results show that singular or fractional IR exposure led to a decrease in spatial memory ability and activity in mice, and the cognitive and motor functions gradually recovered after singular 5 Gy IR in a time-dependent manner, while the fractional 10 Gy IR group could not recover. The decrease in bone density due to the increase in osteoclast number may be relative to the down-regulation of RUNX2, sclerostin, and beta-catenin. Meanwhile, the brain injury caused by IR exposure is mainly linked to the down-regulation of BNDF and Tau. IR exposure leads to memory impairment, reduced activity, and self-recovery, which are associated with time and dose. The mechanism of cognitive and activity damage was mainly related to oxidative stress and apoptosis induced by DNA damage. The damage caused by fractional 10 Gy TBI is relatively stable and can be used as a stable multi-organ injury model for radiation mechanism research and anti-radiation medicine screening.https://www.mdpi.com/1422-0067/25/1/337radiation injuryionizing radiationdelayed radiation damagebrain injurybone loss |
| spellingShingle | Yi Ru Xianxie Zhang Baoying Shen Chunqi Yang Huijing Yu Zuoxu Liu Xiangjun Wu Fangyang Li Jialu Cui Chengcai Lai Yuguang Wang Yue Gao Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice International Journal of Molecular Sciences radiation injury ionizing radiation delayed radiation damage brain injury bone loss |
| title | Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice |
| title_full | Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice |
| title_fullStr | Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice |
| title_full_unstemmed | Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice |
| title_short | Delayed Reaction of Radiation on the Central Nervous System and Bone System in C57BL/6J Mice |
| title_sort | delayed reaction of radiation on the central nervous system and bone system in c57bl 6j mice |
| topic | radiation injury ionizing radiation delayed radiation damage brain injury bone loss |
| url | https://www.mdpi.com/1422-0067/25/1/337 |
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