Dentate Gyrus Neurogenesis After Simulated Weightlessness Of Tail-suspended Model In The Rat

Recently research found: adult central nervous system(CNS) is still able to generate new neurons persistently, neurogenesis still exist at adult CNS, neural stem cell exist at every mammalian's adult nervous system include human's. Hippocampus is an important neurogenesis zone, and is a brain region correlate to study and memory. Formerly study indicated that adult hippocampus neural stem cells are situated in hippocampus dentate gyrus (DG) subgranular zone and innermost layer of granular cell layer, new generated cells from here can differentiate into neuronal cells.The effect of microgracity on brain functions is an important research of space medicine. Exposure to weightlessness may lead to a state of structural and functional alteration. Many organs and systems undergo physiological changes, these include cephalad fluid shift, loss of fluids and electrolytes, loss of muscle mass, reduced immune response, space motion sickness. Neurophysiological problems were also observed, such as alterations of movement/ orientation control, impairment of kinematics and of postural adaptation. As brain is a macrosystem with complex structure and function, its functional status is determined by state of each subsystem and their interaction. The fuction of brain must be change unavoidably under the effect of weightless. In this special environment about weightless, neurogenesis may be effected.In this study, we observed effect of weightlessness on adult rat hippocampus dentate gyrus neurogenesis. In this study, we chose male Sprague-Dawley rats from experiment animal center in FMMU as experimental subjects, using tail-suspended hindlimb-unloaded rat model, The thymidine analog 5-bromodeoxyuridine (BrdU) was injected intraperitoneally at definite time points, with immunohistochemistry staining, we observed new generate cells proliferation and new generate neural stem cell differentiation in the hippocampus dentate gyrus at different time points after simulated weightlessness, as well as microvascular change and new generate vascular endothelial cell proliferation in the hippocampus dentate gyrus at different time points after simulated weightlessness. We investigate initially effects of weightlessness on adult rat hippocampus dentate gyrus neurogenesis and accompanying vascular change, to provide basic experimental evidence for further elucidating characteristic of neurogenesis and biologic mechanisms in dentate gyrus after simulated weightlessness.The main results of present work are as follows:(1) Changes of cell proliferation in the dentate gyrus after simulated weightlessness: BrdU-labeled cell nuclei in the hippocampus DG were irregular in shape and clustered exclusively in the SGZ after simulated weightlessness. After simulated weightlessness treatment, quantitative analysis of BrdU labeling within the SGZ, dentate granule cell layer and hilus revealed a significant decrease in 7 and 14 days after simulated weightlessness treatment in comparison with control rats. The number of BrdU-positive cells in the dentate gyrus rised 28 days after simulated weightlessness. The number of BrdU-positive cells at simulated weightlessness 7 days and 14 days groups is decreased significantly compared with the number of control groups(P < 0. 01).(2) Differentiation of simulated weightlessness-induced neurogenesis in the dentate gyrus: Most BrdU/DCX double labeled cell nuclei dispersed were larger in size than their precursor cells located in the SGZ and round in shape, display characteristic of mature granular cell, whereas BrdU-labeled cells in the SGZ were irregular in shape. BrdU-labeled cells always co-exist neuronal specificity marker NeuN-labeled cells, and seldom coexist gliocyte specificity marker GFAP-labeled cells. The results showed that BrdU-labeled cells differentiate to neurons mostly. The number of BrdU/NeuN double lebeled cells at simulated weightlessness 14 days and 28 days groups is decreased significantly compared with the number of control groups(P < 0.05), The number of BrdU/GFAP double lebeled cells in the dentate gyrus at simulated weightlessness 14 days and 28 days groups has no significantly different compared with the number of control groups (P > 0.05)(3) Microvessel changes in the dentate gyrus after simulated weightlessness: RECA-labeled blood vessels were buffy stained, vessel wall endotheliocyte had clear shape, and the distribution of blood vessels is obvious in branch form. The number of blood vessels at simulated weightlessness 14 days groups is decreased significantly compared with the number of control groups(P < 0. 05), The number of blood vessels at simulated weightlessness 28 days groups has significantly different compared with the number of control groups(P < 0. 05). BrdU and RECA double labeled results showed that BrdU-labeled cells existed in RECA-labeled blood vessel zone, which indicated these cells were new generated endotheliocyte. The number of double-labeled cells at simulated weightlessness 14 days groups is decreased significantly compared with the number of control groups(P < 0. 05), The number of double-labeled cells at simulated weightlessness 28 days groups has significantly different compared with the number of control groups(P < 0. 05). This changes are conformed to that of new generate neural stem cells.In conclusion, this study demonstrates that, effect of simulated weightlessness can suppress cell proliferation, after long-term simulated weightlessness organism may take accommodate mechanism to oppose restrain effect of simulated weightlessness. Simulated eightlessness has no significantly effect on neural stem cell differentiation direction. The effect of simulated weightlessness influence with angiogenesis and neurogenesis may have dependability. On the foundation of above study, we will further observe survival, apoptosis of new generate nerve cell and changes of corresponding vascular endothelial cell with excreting factor levels in the dentate gyrus after simulated weightlessness, as well as corresponding changes in the dentate gyrus after removed simulated weightlessness. The following research must be emphasized on finding if using vascular nutrition factor and neurotrophic factors can improve the suppress level with dentate gyrus neurogenesis after simulated weightlessness, which can provide experimental evidence for further elucidating neurogenesis mechanisms in dentate gyrus after simulated weightlessness.