Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism o...Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism of action remain unclear.Methods In an in vivo study,a low-pressure oxygen chamber was used to simulate high-altitude hypoxia,and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway.Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats,and synaptic damage in the hippocampus and changes in oxidative stress levels were observed.In vitro,SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion(OGD/R)models.Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats,triggered oxidative stress in the hippocampal tissue,and reduced the dendritic spine density of hippocampal neurons.Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress,synaptic damage,and the learning and memory impairment induced by high-altitude exposure.Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.展开更多
Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partl...Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partly because most current methods are based on circular junction counts and overlook the fact that a circRNA is formed from the host gene by backsplicing(BS).To distinguish the expression difference originating from BS or the host gene,we present differentially expressed back-splicing(DEBKS),a software program to streamline the discovery of differential BS events between two rRNA-depleted RNA sequencing(RNA-seq)sample groups.By applying to real and simulated data and employing RT-qPCR for validation,we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups.DEBKS is available at https://github.com/yangence/DEBKS as open-source software.展开更多
基金supported by Beijing Natural Science Foundation(No.7232090)the National Natural Science Foundation of China(82101306)the Scientific and Technological Innovation 2030(2021ZD0201100).
文摘Objective High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory.Nogo-A is an important axonal growth inhibitory factor.However,its function in high-altitude hypoxia and its mechanism of action remain unclear.Methods In an in vivo study,a low-pressure oxygen chamber was used to simulate high-altitude hypoxia,and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway.Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats,and synaptic damage in the hippocampus and changes in oxidative stress levels were observed.In vitro,SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion(OGD/R)models.Results Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats,triggered oxidative stress in the hippocampal tissue,and reduced the dendritic spine density of hippocampal neurons.Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress,synaptic damage,and the learning and memory impairment induced by high-altitude exposure.Conclusion Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.
基金supported by the Beijing Municipal Science and Technology Commission,China(Grant No.Z181100001518005)the Chinese Institute for Brain Research,Beijing,China to EY,the National Natural Science Foundation of China(Grant No.81873769)to CCthe Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center,China(Grant No.BMU2020BSS001)to ZL.
文摘Circular RNAs(circRNAs)are involved in various biological processes and disease pathogenesis.However,only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species,partly because most current methods are based on circular junction counts and overlook the fact that a circRNA is formed from the host gene by backsplicing(BS).To distinguish the expression difference originating from BS or the host gene,we present differentially expressed back-splicing(DEBKS),a software program to streamline the discovery of differential BS events between two rRNA-depleted RNA sequencing(RNA-seq)sample groups.By applying to real and simulated data and employing RT-qPCR for validation,we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups.DEBKS is available at https://github.com/yangence/DEBKS as open-source software.
