title: Effects of expression level of DNA repair-related genes involved in the NHEJ pathway on radiation-induced cognitive impairment.
abstract: 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.
authors.affiliation: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou 215004, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Zhang
authors.forename: Lie-Song
authors.initials: LS
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Ji
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ding
authors.forename: Jia
authors.initials: J
authors.lastname: Wu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology* / Q000528:radiation effects*; D003071:Cognition / Q000528:radiation effects*; D003072:Cognition Disorders / Q000235:genetics*; D059766:DNA End-Joining Repair / Q000235:genetics* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects
chemical_list: D004268:DNA-Binding Proteins