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Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment

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机构: [1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
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关键词: DNA repair DSB radiation XRCC4 XRCC5 XRCC6 cognitive impairments

摘要:
Cranial radiation therapy can induce cognitive decline. Impairments of hippocampal neurogenesis are thought to be a paramountly important mechanism underlying radiation-induced cognitive dysfunction. In the mature nervous system, DNA double-strand breaks (DSBs) are mainly repaired by non-homologous end-joining (NHEJ) pathways. It has been demonstrated that NHEJ deficiencies are associated with impaired neurogenesis. In our study, rats were randomly divided into five groups to be irradiated by single doses of 0 (control), 0 (anesthesia control), 2, 10, and 20 Gy, respectively. The cognitive function of the irradiated rats was measured by open field, Morris water maze and passive avoidance tests. Real-time PCR was also used to detect the expression level of DNA DSB repair-related genes involved in the NHEJ pathway, such as XRCC4, XRCC5and XRCC6, in the hippocampus. The influence of different radiation doses on cognitive function in rats was investigated. From the results of the behavior tests, we found that rats receiving 20 Gy irradiation revealed poorer learning and memory, while no significant loss of learning and memory existed in rats receiving irradiation from 0-10 Gy. The real-time PCR and Western blot results showed no significant difference in the expression level of DNA repair-related genes between the 10 and 20 Gy groups, which may help to explain the behavioral results, i.e. DNA damage caused by 0-10 Gy exposure was appropriately repaired, however, damage induced by 20 Gy exceeded the body's maximum DSB repair ability. Ionizing radiation-induced cognitive impairments depend on the radiation dose, and more directly on the body's own ability to repair DNA DSBs via the NHEJ pathway.

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出版当年[2012]版:
大类 | 4 区 医学
小类 | 3 区 生物学 3 区 核医学
最新[2023]版:
大类 | 4 区 医学
小类 | 3 区 生物学 4 区 肿瘤学 4 区 核医学
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出版当年[2011]版:
Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Q2 BIOLOGY
最新[2023]版:
Q2 BIOLOGY Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Q3 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2011版] 出版当年五年平均 出版前一年[2010版] 出版后一年[2012版]

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第一作者机构: [1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
通讯作者:
通讯机构: [1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
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