| HUANG Guo-dong,LUO Ming,QU Xiao-fei,CHENG Yan-lei,CAI Qian,DONG Xiao-rong,WU Gang.Relationship between impaired hippocampal neurogenesis and cognitive dysfunction induced by cranial radiation therapy[J].Chinese Journal of Radiological Medicine and Protection,2013,33(2):113-118,123 |
| Relationship between impaired hippocampal neurogenesis and cognitive dysfunction induced by cranial radiation therapy |
| Received:September 19, 2012 |
| DOI：10.3760/cma.j.issn.0254-5098.2013.02.001 |
| KeyWords:Irradiation-induced brain injury Hippocampus Neurogenesis Microglia Inflammation |
| FundProject:国家自然科学基金(30800283, 81172595);中国博士后科学基金(201104440);中国博士后科学基金面上项目(20100480905) |
| Author Name | Affiliation | E-mail | | HUANG Guo-dong | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | | | LUO Ming | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | | | QU Xiao-fei | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | | | CHENG Yan-lei | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | | | CAI Qian | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | | | DONG Xiao-rong | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | xr.dong@gmail.com | | WU Gang | Cancer Center, Affiliated Union Hospital, Huazhong University of Science and Technology,Wuhan 430023,China | |
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| Abstract:: |
| Objective To investigate the changes of hippocampal neurogenesis and cognitive dysfunction induced by cranial radiation therapy. Methods C57BL/6J mice aged 10 d were subjected to 10 Gy whole brain irradiation with 6 MV X-rays to develop irradiation-induced brain injury model. Morris water maze was designed to estimate spatial learning and memory. At different time post irradiation, brain tissue was removed to stain with hematoxylin-eosin for the pathological results.DCX and PCNA immunohistochemical staining was used to mark the level of neurogenesis in the hippocampus, and ED1 immunohistochemical staining to mark the activation of microglia. The TUNEL assay was used to assess the apoptotic neuron death in situ in the hippocampus. Real-time PCR was supplied to inspect the expression of TNF-α and IL-1β mRNA. Enzyme Linked Immunosorbent Assay (ELISA) was tested for the concentration of TNF-α in the plasma.Results Pathological studies demonstrated that radiation could induce interstitial edema, inflammatory cell infiltration, cell degeneration, necrosis, apoptosis in the acute phase, edema subsiding, reduction of inflammatory cells, and cytothesis in the dentate gyrus of the hippocampus. IHC studies revealed that, at different time post irradiation, the number of DCX-positive cells and PCNA-positive cells decreased(F=4.9-12.5,5.2-15.7,P<0.05) but ED1-positive cells increased significantly (F=20.8, P<0.05). TUNEL-positive cells began to appear in the dentate gyrus of hippocampus 6 h post-irradiation, and its number reached to the highest level at 48 h post-irradiation (F=15.1, P<0.05). The formation of γ-H2AX foci got at the top 0.5 h post-irradiation (F=18.4, P<0.05) and then decreased. After irradiation, the expressions of TNF-α and IL-1β mRNA in the the irradiated group was higher than those of the control group (t=16.3,12.7, P<0.05). The concentration of TNF-α in the plasma of the irradiated group was higer than that in the control group 3 h post-irradiation, and maximized at 1 week post-irradiation (F=10.5, P<0.05). Morris water maze tests showed that the latency had no significant differences between the irradiated group and the control group at 1, 2, 3 d post-irradiation, but the latency in the irradiated group was longer than that in the control group with a significant differences at 4, 5, 6 d post-irradiation (F=7.01, 8.17, 4.22, P<0.05).Conclusions Irradiation-induced cognitive dysfunction may be caused by microglial activation and suppression in hippocampal neurogenesis following cranial radiation therapy. |
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