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Introduction In recent years, people have found that neural stem cells still exist in human and animals after the development and these neural stem cells can constantly generate new neurons and astrozytes in life span.In most adult mammalian CNS, active neurogenesis occurs throughout life in the subventricular zone (SVZ) of the lateral ventricle and in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus.However, the mechanisms of proliferation, differentiation and survival about adult neurogenesis remain unclear.It has been found that experimental changes of living environment can significantly affect the proliferation, differentiation and survival of neural stem cells in the SGZ of the dentate gyrus.However, it has not been reported that how the changes of natural environment affect the adult neurogenesis.Objective The aim of our study is to investigate the influence of high-altitude living environment in the Qinghai-Tibet Plateau on the proliferation and differentiation of adult neural stem cells in the SGZ of the dentate gyms in mice, and we expect that the results of our experiment can provide evidences for elucidating the mechanism of adult neurogenesis.Methods Healthy adult Kunming mice were divided into 2 groups: one altitude of control group is 1500 m in Lanzhou, the other altitude of experimental group is 4600 m in Tuotuohe on Qinghai-Tibet Plateau.To label the newly generated cells 5-bromine deoxidizing urine nucleoside (BrdU, 50 mg/kg) were injected intraperitoneally for 6 times within 3 d.Single immunocytochemistry against BrdU and double immunocytochemistry against BrdU and Prox-1 were performed.Finally, the newly generated BrdU-postive cells and double labeled ceils for BrdU and Prox-1 were counted in laser confocal microsopy photographs, respectively.Results The BrdU-positive cells of experimental group significantly reduced to 60% compared with the control group (P =0.001), indicating that the high-altitude (low oxygen) environment inhibit the proliferation of adult neural stem cells in dentate gyrus of mice.The percentage of BrdU/Prox-1 double labeled positive cells in BrdU-positive cells showed no significant differences between the experimental group and the control group (P =0.211), indicating that the differentiation of newly generated cells were not influenced by the high-altitude environment.More than 90% Brdu-positive cells in dentate gyrus were prox-1-postive, indicating that most of the newly generated cells differentiated into granule cells (neurons).Conclusion In the high-altitude and low oxygen environment of the Qinghai-Tibet Plateau, the proliferation of neural stem cells in the SGZ of the dentate gyrus of mice is significantly decreased.However their rate of differentiation to the granule cells is not significantly affected.Therefore these changes may helps the animals adapt to the high altitude surroundings.