The Research Of Central Neural System Of Rats Model Localized-⁵⁶Fe²⁶⁺ Heavy Ion Radiation Induced Damage Effects

With the rapid development of Chinese Manned space flight,more and more projects such as the first manned moon landing and send a probe to Mars provide both chances and challenges for space life science research.Especially,the astronant have to face a seriously security issue in the long-term manned space flight.The astronant is influenced by so many factors in the space environment,which include radiation,microgravity,sub-magnetic field,claustrophobic environment,circadian variation rhythm and etc.Besides,the impairment of radiation to human body becomes one of the central issues in space life science and the heavy ion radiation plays a key role in the damage effect of radiation because of it’s accumulation effect,strong impairment as well as difficult protection.Though the heavy ion radiation’s proportion is not high in the radiation,the heavy ion radiation poses a great threat to the security of astronant during the long flights.However,current studies related to biological effects of space heavy ion radiation mainly focus on the relative low dose,whole body irradiation,short term and superimposed effects,which pay more attention on phenomenon rather than mechanism about the damage effect of heavy ion radiation.Moreover,based on the result of my research group and study about the long time effect of space heavy ion radiation,we establish the ⁵⁶Fe²⁶⁺heavy ion sourced radiation and SD rat were used to establish the local brain radiation model,the dose of radiation is 3.4Gy and8Gy respectively,at the same time.we select 1,2 as well as 3 month afte radiation as the detection time point and the behavioral experiment.PET scan of the glucose metabolism in the brain,pathological section together with the transcriptomic as the method to discuss the mechanism of damage effect.Basing on the above research,results of this project are summarized as following.Firstly,the data of behavioral experiment shows the body ability has been constantly changed after ⁵⁶Fe²⁶⁺radiation.We choose open field test,rotary rod fatigue test,sugar water test and morris water maze as the behavioral experiment to analysis the SD rats model after heavy ion radiation in 1,2,3 month.After 1 month,the 3.4Gy group showed a disability on physicalexercising in the rotary rod fatigue test and the promotion of explore level and anxiety in the openfield test.After 2 month,the 3.4Gy group showed a disability on physical exercising in the rotary rod fatigue test and the promotion of physical activity and anxiety in the open field test.simultaneously,After 3 month,the 3.4 Gy group showed a disability on physical exercising in the rotary rod fatigue test,the promotion of explore level and anxiety in theopen field test and the weakness of learning and memory ability in the morris water maze.At the time of 2 month,the 8 Gy group showed a disability on physical exercising in the rotary rod fatigue test,the promotion of physical activity and anxiety in the open field test,the preference to sugar water in the sugar water test as well as the weakness of learning and memory ability in the morris water mazeSecondly,PET scan of the glucose metabolism in the brain at the 1,2 3 month showed the diversification of glucose metabolism in the brain after ⁵⁶Fe²⁶⁺radition and different brain regions’glucose metabolism has increased or decreased.Besides,the level of glucose metabolism in the 3.4Gy group‘s striatum has been persistently changed in the 1,2,3 month,which up-regulate in 1,2 month and down-regulate in 3 month（P<0.01）.Morever,the changes of glucose metabolism’s area in brain showed a dynamic change with time.which indicates that the time increases,the area decreases.Namely,theheavy ion radiation make the long term change about the glucose metabolism in the SD rat’s brain.Thirdly,the analysis of pathological section indicated that after 1 month,3.4Gy group‘s striatum showed visible vacuoles and after 2 month,part of the sample in the 8Gy group showed the necrosis of the piriform cortex and formation of a softening lesion,the cell degeneration and focal calcification of neurons and glial in the area of thalamus and hypothalamus,visible vacuoles in the striatum.Fourthly,combined with the results of behavioral experiment.PET scan of the glucose metabolism in the brain and pathological section,we found that different regions of rat’s brain got various sensitivity after the heavy ion radiation.which may caused by the different ratio of neurons and glial,the various ability about the neurogenesis and the diversity type of glucose metabolism pathway in distinct area of brain.Meanwhile,the striatum showed a interesting result in behavioral experiment.PET scan of the glucose metabolism in the brain and pathological section,which balances the stability of voluntary movement and maintenance of muscle tension.Fifthly,according to the analysis of KEGG,the data of striatum‘s transcriptomic states the differential genes may take part in the following pathway to adapt to the damage effect and repairment after radition.After 1 month,the change of gene in 3.4Gy group‘s striatum may regulate Synaptic vesicle cycle pathway,Complement and coagulation cascades pathway,Endocytosis pathway,SNARE interactions in vesicular transport pathway,Cell adhesion molecules（CAMs）pathway,Pentose and glucuronate interconversions pathway,Ether lipid metabolism pathway,Phagosome pathway,Endocrine and other factor-regulated calcium reabsorption pathway,Starch and sucrose metabolism pathway,mTOR signaling pathway,Neuroactive ligand-receptor interaction pathway,Gap junction pathway,GABAergic synapse pathway,Protein digestion and absorption pathway,Antigen processing and presentation pathway,Inflammatory mediator regulation of TRPchannelspathway,Glutamatergicsynapsepathway,HIF-1signaling pathway,Serotonergic synapse pathway,Calcium signaling pathway,cAMP signaling pathway and PI3K-Akt signaling pathway.After 2 month,the change of gene in 3.4Gy group‘s striatum may regulate the Antigen processing and presentationCell adhesion molecules（CAMs）pathway,Phagosomepathway,Endocytosispathway,Cytosolic DNA-sensingpathway,RIG-I-likereceptor signaling pathway,mTOR signaling pathway,Adipocytokine signaling pathway,Toll-like receptor signaling pathway,Melanogenesis pathway,Pancreatic secretion pathway,HIF-1 signaling pathway,Insulin signaling pathway,cGMP-PKG signaling pathway,Calcium signaling pathway,cAMP signaling pathway,Proteoglycans in cancer and PI3K-Akt signaling pathway.After 2 month,the change of gene in 8 Gy group‘s striatum may regulate the mTOR signaling pathway,Adipocytokine signaling pathway,HIF-1 signaling pathway,Insulin signaling pathway,Proteoglycans in cancer and PI3K-Akt signaling pathway.After 3 month,the change of gene in 3.4Gy group‘s striatum may regulate the Pentose and glucuronate interconversions pathway,Ether lipid metabolism pathway,Endocrine and other factor-regulated calcium reabsorption pathway,Synaptic vesicle cycle pathway,Complement and coagulation cascades pathway,Glutamatergic synapse pathway,Leukocyte transendothelial migration pathway,Fox O signaling pathway,Tight junction pathway,Cell adhesion molecules（CAMs）pathway and PI3K-Akt signaling pathway.Above all,PI3K-Akt signaling pathway sustained in 1,2,3 month after radition in both 3.4Gy group and 8Gy group.Besides,the mTOR signaling pathway was expres expressed in 1 and 2month in all the groups.And many pathways related to glucose metabolism may lead to the change of striatum.The HIF-1 signaling pathway may induced by the low oxygen environmental factors through the radiation damage effect.On the basis of GO data,from the view of time effect,in 1 month,the different gene may take part in the ion transport、anion transport、transporter activity、organic anion transport、localization、substrate-specific transporter activity、single-organism transport、modified amino acid transport、multicellular organismal development、developmental process、amino acid transport、ion transmembrane transporter activity、anion transmembrane transporter activity、regulation of biological quality、chemical homeostasis、substrate-specific transmembrane transporter activity、metal ion transport、system development、single-organism developmental process、multicellular organismal response to stress、transport、transmembrane transporter activity、ion homeostasis biological process,molecular function and cellular component（pValue<0.05）,in 2 month,the different gene may take part in the MHC protein complex、antigen processing and presentation of peptide antigen、antigen binding biological process,molecular function and cellular component（pValue<0.1）,in 3 month,the different gene may take part in the anion transport、organic anion transport、anion transmembrane transporter activity、transporter activity、ion transport、modified amino acid transport、cellular monovalent inorganic cation homeostasis、memory、regulation of biological quality、substrate-specific transporter activity、monovalent inorganic cation homeostasis、amino acid transport、cerebrospinal fluid secretion、regulation of intracellular pH、thyroid hormone transport、regulation of cellular pH、brush border membrane、secondary active transmembrane transporter activity、single-organism developmental process、regulation of pH、response to glucocorticoid stimulus、response to corticosteroid stimulus biological process,molecular function and cellular component（pValue<0.05）.From the view of dose effect,in 2 month,there is no significant difference between 8G and 0Gy as well as 3.4Gy and 8Gy,besides,the different gene between 3.4Gy and 0Gy may take part in the MHC protein complex、antigen processing and presentation of peptide antigen、antigen binding biological process,molecular function and cellular component（pValue<0.1）.All of these biological processes and pathways may provide a definition of the results from behavioral experiment,PET scan and pathological section.In a word,research about the injury in central nervous system and its effects under simulated space heavy ion radiation condition in the manned space flight is conducive to deeply understand the mechanism of space radiation risk and injury-relevant evaluation and prevention,as well as further clarification of whole-body irradiation induced overlapping effect.Theoretical foundation may be supplied to the early warning system in space radiation.What’s more,this project also has theoretical value and application prospect to the key state science and technology projects,such as the establishment of manned orbital station,human lunar exploration and Mars probes launch.In addition,this project may provide a better reference resource to the clinical application.of the cancer radiotherapy technique by using heavy ions.