Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Postpartum depression （PPD） is a modified form of major depressive disorders （MDD） that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infa...Postpartum depression （PPD） is a modified form of major depressive disorders （MDD） that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys （Macaca fascicularis） living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum （BDP） as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups： A t3DP group （n=6）, which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group （n=4）. The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction--similar to humans--as well as much greater homology to humans than rodents. As such,展开更多
目的：建立并验证流式细胞法检测食蟹猴外周血淋巴细胞亚群（辅助性 T 细胞、细胞毒性 T 细胞、B细胞、NK 细胞）的方法，建立正常参考值范围，比较性别和年龄差异。方法 EDTA‐K2抗凝管采集食蟹猴血样，采用两组三色荧光抗体组合 CD3‐...目的：建立并验证流式细胞法检测食蟹猴外周血淋巴细胞亚群（辅助性 T 细胞、细胞毒性 T 细胞、B细胞、NK 细胞）的方法，建立正常参考值范围，比较性别和年龄差异。方法 EDTA‐K2抗凝管采集食蟹猴血样，采用两组三色荧光抗体组合 CD3‐FITC／CD4‐PerCP／CD8‐PE 、CD3‐PE‐CYTM 5．5／CD16‐PE／CD20‐FITC 进行细胞分类检测。测定批内差异和批间差异以考察方法精密度；并分别对血样室温放置6 h ，4℃放置24 h ，检测处理后样本4℃放置24h 的样品稳定性进行考察。进一步扩大检测样本数量，确立不同性别、年龄段的正常参考值范围，并比较性别和年龄差异。结果精密度检测各指标批内变异度为2．51％～12．51％，批间变异度为1．32％～8．63％。血样经不同处理和放置不同时间后的测定结果与新鲜采集血样后的检测结果偏差均小于10％。确立了1．5～2岁和3～5岁两个年龄段，雌雄食蟹猴淋巴细胞亚群的正常参考值。比较发现，3～5岁与1．5～2岁相比，外周血 NK 细胞（CD3－ CD16＋）亚群比例升高；B 淋巴细胞（CD3－ CD20＋）亚群有年龄和性别差异。结论食蟹猴外周血淋巴细胞亚群检测的血液样本在室温放置6 h ，4℃放置24 h 内检测，或处理后4℃放置24 h 内检测，结果稳定性良好。不同年龄段和性别食蟹猴的淋巴细胞亚群正常值范围具有差异，提示选择食蟹猴进行相关研究评价时应予以注意。展开更多
In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys using individualized low-dose MPTP, to explore effective indicators for the early prediction of clinical outcomes. MPTP was not stopped...In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys using individualized low-dose MPTP, to explore effective indicators for the early prediction of clinical outcomes. MPTP was not stopped until the animals showed typical PD motor symptoms on days 10 to 13 after MPTP administration when the Kurlan score reached 10; this abrogated the dif- ferences in individual susceptibility to MPTP. The clinical symptoms persisted, peaking on days 3 to 12 after MPTP withdrawal （rapid progress stage）, and then the Kurlan score plateaued. A Kurlan score at the end of the rapid progress stage 〉15 reflected stable or slowly-progressive PD, while a score 〈15 indicated spontaneous recovery. The entire clinical evolution and outcome of the systemic PD model was characterized in this study, thus providing options for therapeutic and translational research.展开更多
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金supported by National Natural Science Foundation of China(31271167,81271495,31070963,30921064)the Yunnan Provincial Project to attract ore-hundred exceptional talents from Overseas
文摘Postpartum depression （PPD） is a modified form of major depressive disorders （MDD） that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys （Macaca fascicularis） living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum （BDP） as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups： A t3DP group （n=6）, which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group （n=4）. The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction--similar to humans--as well as much greater homology to humans than rodents. As such,
文摘目的：建立并验证流式细胞法检测食蟹猴外周血淋巴细胞亚群（辅助性 T 细胞、细胞毒性 T 细胞、B细胞、NK 细胞）的方法，建立正常参考值范围，比较性别和年龄差异。方法 EDTA‐K2抗凝管采集食蟹猴血样，采用两组三色荧光抗体组合 CD3‐FITC／CD4‐PerCP／CD8‐PE 、CD3‐PE‐CYTM 5．5／CD16‐PE／CD20‐FITC 进行细胞分类检测。测定批内差异和批间差异以考察方法精密度；并分别对血样室温放置6 h ，4℃放置24 h ，检测处理后样本4℃放置24h 的样品稳定性进行考察。进一步扩大检测样本数量，确立不同性别、年龄段的正常参考值范围，并比较性别和年龄差异。结果精密度检测各指标批内变异度为2．51％～12．51％，批间变异度为1．32％～8．63％。血样经不同处理和放置不同时间后的测定结果与新鲜采集血样后的检测结果偏差均小于10％。确立了1．5～2岁和3～5岁两个年龄段，雌雄食蟹猴淋巴细胞亚群的正常参考值。比较发现，3～5岁与1．5～2岁相比，外周血 NK 细胞（CD3－ CD16＋）亚群比例升高；B 淋巴细胞（CD3－ CD20＋）亚群有年龄和性别差异。结论食蟹猴外周血淋巴细胞亚群检测的血液样本在室温放置6 h ，4℃放置24 h 内检测，或处理后4℃放置24 h 内检测，结果稳定性良好。不同年龄段和性别食蟹猴的淋巴细胞亚群正常值范围具有差异，提示选择食蟹猴进行相关研究评价时应予以注意。
基金supported by grants from the National High-Tech Development Project of Ministry of Sciences and Technology of China(2012AA020703)the National Natural Science Foundation of China(31472056)+1 种基金Scientific Project of the Science and Technology Department of Guangxi Zhuang Autonomous Region,China(1598025-31)Scientific Project of the Science and Technology Bureau of Nanning Municipality,Guangxi Zhuang Autonomous Region,China(20145194,20155192)
文摘In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys using individualized low-dose MPTP, to explore effective indicators for the early prediction of clinical outcomes. MPTP was not stopped until the animals showed typical PD motor symptoms on days 10 to 13 after MPTP administration when the Kurlan score reached 10; this abrogated the dif- ferences in individual susceptibility to MPTP. The clinical symptoms persisted, peaking on days 3 to 12 after MPTP withdrawal （rapid progress stage）, and then the Kurlan score plateaued. A Kurlan score at the end of the rapid progress stage 〉15 reflected stable or slowly-progressive PD, while a score 〈15 indicated spontaneous recovery. The entire clinical evolution and outcome of the systemic PD model was characterized in this study, thus providing options for therapeutic and translational research.
