The Role Of TrkA/TrkB In Radiation-induced Hippocampal Neurogenesis Impairment

Objective Radiotherapy is one of the important methods for the treatment of primary and secondary brain tumors.As a result,treatment-related long-term adverse reactions are gaining further attention.Among them,the incidence of cognitive dysfunction after cranial irradiation increased year by year,seriously affecting the quality of life after treatment of patients,which has become the focus of the current study.Neurogenesis in the hippocampus of the brain plays a key role in the process of altering the plasticity of the nerve,but so far the pathogenesis of neurotoxicity is still unclear by ionizing radiation.Therefore,the aim of this study was to investigate the effects of ionizing radiation on neurogenesis and TrkA and Trk B protein expression in hippocampus of rats,in order to study its possible mechanismMethods Fifty six 21-day old 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 ?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 precursors prolifration.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 precursors prolifration comparing with control group(t=6.49,P<0.05).Protein levels of TrkA expressions increased significantly(t=2.64?3.06?4.80?2.64,P<0.05)while the levels of TrkB expressions decreased significantly(t =4.59?3.06?2.81?2.57,P<0.05);the mRNA levels of TrkA expressions increased significantly(t =4.57 ? 3.06 ? 5.39 ? 5.86,P<0.05)while the levels of TrkB expressions decreased significantly(t =14.87?11.69?4.98,P<0.05).Conclusion Under this experimental condition,the expression of TrkA and Trk B,which is an important downstream signal of NGF and BDNF,may play an important role in the injury of hippocampal neurogenesis induced by ionizing radiation.After the whole brain irradiation,the number of proliferating neurons and the size and morphology of dendritic spines were significantly changed,which may be related to the expression of TrkA and Trk B after whole brain irradiation.By interfering with the expression of TrkA and TrkB may improve injury of hippocampal neurogenesis induced by ionizing radiation.