Ionizing Irradiation Induce Cognitive Dysfunction By Increasion ProBDNF In The Mouse Hippocampus

Objective:To observe the effect of ionizing irradiation on cognitive and the expression of hippocampal proBDNF signaling in mice.Methods:Forty adult Kunming mice were randomly divided into control group and irradiation group.The irradiation group mice were irradiated with a single ¹³⁷Cs-?rays at an absorbed dose of 4 Gy.5 weeks after irradiation,the Novel Place Recognition test and Y-maze test were used to evaluate the cognitive function of mice;Expression of BDNF,p75NTR,Sortilin,Sorcs2 and FSTL4 mRNA in the hippocampus were detected by RT-PCR;The expression of neurogenesis marker DCX in the hippocampus was determined by immunohistochemistry;Expression of BDNF,proBDNF,MMP-9,tPA,p75NTR,Sortilin,Sorcs2,FSTL4,SYN-1,Synaptophysin,NeuN,Bcl2,PARP and Caspase-3 protein in the hippocampus were assayed by Western blot.Results:Compared with the control group mice,1.irradiation group mice showed significantly reduced discrimination ratio in the Novel Place Recognition test?P<0.05?and reduced spontaneous alternation in the Y-maze test?P<0.05?;2.irradiation group mice showed no effect on the expression of BDNF mRNA level in the hippocampus?P>0.05?;3.irradiation group mice showed significantly down-regulated expression of BDNF protein level in the hippocampus,up-regulated expression of proBDNF protein level?P<0.05?and reduced ratio of BDNF to proBDNF in the hippocampus?P<0.05?;4.irradiation group mice showed remarkably reduced expression of MMP9 protein level in the hippocampus?P<0.05?,but had no effect on the expression of tPA protein level in the hippocampus?P>0.05?;5.irradiation group mice showed significantly down-regulated expression of Sortilin and Sorcs2 mRNA and protein levels in the hippocampus?P<0.05?,but had no effect on the expression of p75NTR mRNA and protein levels in the hippocampus?P>0.05?;6.irradiation group mice showed significantly up-regulated expression of FSTL4 mRNA and protein levels in the hippocampus?P<0.05?;7.irradiation group mice showed significantly reduced number of DCX positive cells in the dentate gyrus of hippocampus?P<0.05?;8.irradiation group mice showed significantly down-regulated expression of SYN-1 and Synaptophysin protein levels in the hippocampus?P<0.05?;9.irradiation group mice showed significantly down-regulated expression of NeuN protein level and Bcl2 protein level in the hippocampus?P<0.05?,while up-regulated expression of PARP and Caspase-3 protein levels in the hippocampus?P<0.05?.Conclusion:Ionizing irradiation could activate hippocampal proBDNF/FSTL4 signaling and lead to neuronal apoptosis,suppressed neurogenesis and impaired synaptic plasticity,which might be contributed to the cognitive dysfunction in mice.