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Objective:To explore the changes of dendritic spine morphology and structure in dentate gyrus(DG) and CA1 areas of hippocampus of young rats, so as to provide a direct morphological basis for studying the molecular mechanism of radiation cognitive impairment.Methods:21-day-old Sprague-Dawley (SD) rats were given a single dose of 10 Gy whole brain irradiation. The changes of cognitive function, dendritic spine density and morphological changes in DG and CA1 areas of hippocampus were observed 1 and 3 months after irradiation, and the expression of postsynaptic density protein (PSD95) was detected by Western blot.Results:The cognitive impairment was observed in young rats 3 months after irradiation. The density of dendritic spines in DG area of hippocampus was decreased significantly by 39.06% and 29.27% at 1 and 3 months after irradiation ( t=14.96, 12.35, P<0.05), respectively. The density of dendritic spines in the basal dendrites of hippocampal CA1 area was decreased by 33.40% ( t=10.39, P<0.05) 1 month after irradiation, but had no significant change at 3 months after irradiation. While the density of dendritic spines in the apical dendrites of CA1 region did not change significantly at 1 and 3 months after irradiation. In addition, the morphology of dendritic spines in DG and CA1 regions of hippocampus was dynamically changed after irradiation. The expression of PSD95 protein was decreased by 24.6% and 50.5% ( t=2.97, 9.27, P<0.05) at 1 and 3 months after irradiation, respectively. Conclusions:This study reported the density and morphological changes of dendritic spines in different brain regions of hippocampus of young rats after ionizing radiation, suggesting that PSD95 may participate in the occurrence of radiation-induced cognitive impairment by affecting the structure and morphology of dendritic spines and reducing synaptic plasticity.
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Objective@#To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment.@*Methods@#Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed.@*Results@#Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05). Immunofluorescent staining showed that the quantity of BrdU+ NeuN+ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01). After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected.@*Conclusion@#p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.
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Objective To investigate the roles of TrkA and TrkB in radiation-induced hippocampal neurogenesis impairment.Methods Fifty-six rats were randomized into radiation group and sham control group.Radiation group received whole brain irradiation at a single dose of 10 Gy.The hippocampus were separated from rats in day 1,day 3,day 14 and 1 month after irradiation.Western blot and RT-PCR were applied to detect the protein levels and mRNA levels.Golgi staining was used to observe the dendritic spine of hippocampus.Immunofluorescence was performed to detect neural precursor's proliferation.Results Compared with control group,the numbers of dendritic spine significantly decreased after irradiation and its shape change obviously.Immunofluorescence showed a significant decrease in neural precursor's proliferation comparing with control group (t =6.49,P ＜ 0.05).Protein level of TrkA expression increased (t =2.64,3.06,4.80,2.64,P ＜ 0.05),while the levels of TrkB protein expression decreased significantly (t =4.59,3.06,2.81,2.57,P ＜ 0.05).The mRNA level of TrkA expressions increased (t =4.57,3.06,5.39,5.86,P ＜ 0.05),while the mRNA level of TrkB decreased (t =14.87,11.69,4.98,P ＜ 0.05).Conclusions As a signaling pathways downstream of NGF and BDNF,TrkA and TrkB may play an important role in radiation-induced neurogenesis impairment.
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Objective:To explore the possible mechanism of astragaloside involved in the mouse podocytes injury induced by TGF-β1 in vitro.Methods:Mouse podocytes were cultured in vitro and then all cell were divided into 5 groups:normal control group , TGF-β1 treatment group ,TGF-β1 treatment +astragaloside low dose group ,TGF-β1 treatment +astragaloside middle dose group and TGF-β1 treatment +astragaloside high dose group.The proliferation rate of each group was investigated by MTT assay ,the expression of TRPC6 protein and mRNA were measured by Western blot and RT-PCR respectively after 48 hours.Results:TGF-β1 can significantly inhibit the proliferation of podocytes ( P<0.05) ,fusions of foot processes or even effaced of podocytes were observed .TGF-β1 could also increase the expression of TRPC6.Astragaloside could reduce the inhibition of TGF-β1 to the proliferain of podocytes significantly ,make the cell shape tend to be normal,and reduce the expression of TRPC6 mRNA and protein with dose-effect relation.Conclusion:TRPC6 play an impor-tant role in the TGF-β1 induecd podocytes injury .Astragaloside can alleviate podocytes injury by reduce the expression of TRPC 6.
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Objective To explore the effects of various radiation doses on the NFAT3/c4 signaling pathway and the improvement effect of exogenous brain-derived neurotrophic factor(BDNF)on this pathway. Methods Four groups of one-month-old Sprague-Dawley rats received radiation doses of 0,2,10,and 20 Gy, respectively, in a single radiation. At three days after radiation, exogenous BDNF was injected stereotaxically into the bilateral hippocampus. Western blotting and RT-PCR were used to assess the levels of NFAT3/c4-related proteins in the hippocampus. Results The results of Western blotting and RT-PCR showed that the level of NFAT3/c4 was reduced in a dose-and time-dependent manner after ionizing radiation. Compared with the radiation alone group,the ionizing radiation plus BDNF group had significantly increased levels of NFAT3/c4 and CaN with increases in radiation dose and time. Conclusions Whole brain radiotherapy inhibits the CaN/NFAT3/c4 signaling pathway. Exogenous BDNF can promote the NFAT-dependent transcription and then improve the cognitive function.