Background Obstructive sleep apnea （OSA） can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer＇s disease （AD）. Chronic exposure to intermittent hypoxia （IH）,...Background Obstructive sleep apnea （OSA） can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer＇s disease （AD）. Chronic exposure to intermittent hypoxia （IH）, such as encountered in OSA, is marked by neurodegenerative changes in rat brain. We investigated the change of thioredoxin （Trx）, spatial learning and memory in rats exposed to chronic intermittent hypoxia （CIH）. Methods Forty healthy male Sprague-Dawley （SD） rats were randomly divided into four groups of ten each： a CIH＋normal saline （CIH＋NS group）, a N-acetylcystein-treated CIH （CIH＋NAC） group, a sham CIH group （sham CIH＋NS）, and a sham NAC-treated sham CIH （CIH＋NAC） group. Spatial learning and memory in each group was assessed with the Morris water maze. Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） method was used to detect the apoptotic cells of the hippocampus CA1 region. Results CIH-rats showed impaired spatial learning and memory in the Morris water maze, including longer mean latencies for the target platform, reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant. Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus, meanwhile, an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH. The rats, which acted better in the Morris water maze, showed higher levels of the Trx mRNA and protein in the hippocampus; apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels. Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.展开更多
Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,ha...Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,has been shown to prevent cerebral ischemic injury.However,the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions（O_2-（·-））.Here,we report that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine,a novel small-molecule compound structurally related to edaravone,showed a stronger inhibitory effect on oxidative stress in vitro.In vivo,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde,two proteins crucial for oxidative stress,suggesting a strengthened antioxidant system.Moreover,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability.Then,we found that 2-methyl-5 Hbenzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone.More importantly,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period,indicating enhanced neuroprotection,sensorimotor function and spatial memory.Together,these findings suggest that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.展开更多
Wheat is an important agricultural crop in the Loess region of China, where there is drought stress and low availability of soil nitrogen and phosphorus. Using a pulse modulation fluorometer, we studied the effects of...Wheat is an important agricultural crop in the Loess region of China, where there is drought stress and low availability of soil nitrogen and phosphorus. Using a pulse modulation fluorometer, we studied the effects of water, nitrogen, and phosphorus on the kinetic parameters of chlorophyll fluorescence in winter wheat. The wheat was grown in layered columns of Eum-Orthic Anthrosol （Cinnamon soil）, with the water content and nutrient composition of each layer controlled. The results showed that the kinetic parameters of chlorophyll fluorescence were sensitive to water stress. The basic fluorescence （F0） of leaves was higher in the dry treatment （0-30 cm layer at 40-45% of field capacity, 30-90 cm at 75-80% of field capacity） compared to the wet treatment （entire soil column at 75-80% of field capacity）. The maximal fluorescence （Fm）, the variable fluorescence （Fv）, the photochemical efficiency （Fv/Fm） and potential activites （Fv/F0） of photosystem 2 （PS2） were significantly lower in the dry treatment. Although drought stress impaired PS2 function, this effect was significantly ameliorated by applying P or NP fertilizer, but not N alone. P application increased FJFm, both in well-watered and water stressed plants, especially when fertilizer was applied throughout the column or within the top 30 em of soil. A combined fertilizer improved photosynthesis in well watered plants, with Fm and F,fFm being the highest when fertilizer was applied throughout the columns. For drought stressed, plants FJFm was significantly greater when combined fertilizer was added within the top 30 cm of soil. We concluded that, when growing winter wheat in both arid and semi-arid parts of the Loess region of China, it is important to guarantee the nutrient supply in the top 30 cm of the soil.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81070067）.
文摘Background Obstructive sleep apnea （OSA） can cause cognitive dysfunction and may be a reversible cause of cognitive loss in patients with Alzheimer＇s disease （AD）. Chronic exposure to intermittent hypoxia （IH）, such as encountered in OSA, is marked by neurodegenerative changes in rat brain. We investigated the change of thioredoxin （Trx）, spatial learning and memory in rats exposed to chronic intermittent hypoxia （CIH）. Methods Forty healthy male Sprague-Dawley （SD） rats were randomly divided into four groups of ten each： a CIH＋normal saline （CIH＋NS group）, a N-acetylcystein-treated CIH （CIH＋NAC） group, a sham CIH group （sham CIH＋NS）, and a sham NAC-treated sham CIH （CIH＋NAC） group. Spatial learning and memory in each group was assessed with the Morris water maze. Real-time PCR and Western blotting were used to examine mRNA and protein expression of Trx in the hippocampus tissue. The terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） method was used to detect the apoptotic cells of the hippocampus CA1 region. Results CIH-rats showed impaired spatial learning and memory in the Morris water maze, including longer mean latencies for the target platform, reduced numbers of passes over the previous target platform and a smaller percentage of time spent in the target quadrant. Trx mRNA and protein levels were significantly decreased in the CIH-hippocampus, meanwhile, an elevated apoptotic index revealed apoptosis of hippocampal neurons of rats exposed to CIH. The rats, which acted better in the Morris water maze, showed higher levels of the Trx mRNA and protein in the hippocampus; apoptotic index of the neurons in the hippocampus of each group was negatively correlated with the Trx mRNA and protein levels. Conclusion The Trx deficit likely plays an important role in the impaired spatial learning and memory in the rats exposed to CIH and may work through the apoptosis of neurons in the hippocampus.
基金supported by grants from NationalNatural Science Foundation of China(31530091,91232304)National Key Research and Development Program of China(2016YFC1306703)+1 种基金Natural Science Foundation of Jiangsu Province(BK20140905)by the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine
文摘Oxidative stress plays an indispensable role in the pathogenesis of cerebral ischemia.Inhibiting oxidative stress has been considered as an effective approach for stroke treatment.Edaravone,a free radical scavenger,has been shown to prevent cerebral ischemic injury.However,the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions（O_2-（·-））.Here,we report that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine,a novel small-molecule compound structurally related to edaravone,showed a stronger inhibitory effect on oxidative stress in vitro.In vivo,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde,two proteins crucial for oxidative stress,suggesting a strengthened antioxidant system.Moreover,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased blood brain barrier permeability.Then,we found that 2-methyl-5 Hbenzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine had a stronger neuroprotective effect than edaravone.More importantly,2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period,indicating enhanced neuroprotection,sensorimotor function and spatial memory.Together,these findings suggest that 2-methyl-5 H-benzo[d]pyrazolo[5,1-b][1,3]oxazin-5-imine could be a preferable option for stroke treatment.
基金supported by the National Natural Science Foundation of China (NSFC 50809068)the foundation of the State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau,China (10502)+1 种基金the China Postdoctoral Science Foundation (20080441196)the West Light Foundation of the Chinese Academy of Science
文摘Wheat is an important agricultural crop in the Loess region of China, where there is drought stress and low availability of soil nitrogen and phosphorus. Using a pulse modulation fluorometer, we studied the effects of water, nitrogen, and phosphorus on the kinetic parameters of chlorophyll fluorescence in winter wheat. The wheat was grown in layered columns of Eum-Orthic Anthrosol （Cinnamon soil）, with the water content and nutrient composition of each layer controlled. The results showed that the kinetic parameters of chlorophyll fluorescence were sensitive to water stress. The basic fluorescence （F0） of leaves was higher in the dry treatment （0-30 cm layer at 40-45% of field capacity, 30-90 cm at 75-80% of field capacity） compared to the wet treatment （entire soil column at 75-80% of field capacity）. The maximal fluorescence （Fm）, the variable fluorescence （Fv）, the photochemical efficiency （Fv/Fm） and potential activites （Fv/F0） of photosystem 2 （PS2） were significantly lower in the dry treatment. Although drought stress impaired PS2 function, this effect was significantly ameliorated by applying P or NP fertilizer, but not N alone. P application increased FJFm, both in well-watered and water stressed plants, especially when fertilizer was applied throughout the column or within the top 30 em of soil. A combined fertilizer improved photosynthesis in well watered plants, with Fm and F,fFm being the highest when fertilizer was applied throughout the columns. For drought stressed, plants FJFm was significantly greater when combined fertilizer was added within the top 30 cm of soil. We concluded that, when growing winter wheat in both arid and semi-arid parts of the Loess region of China, it is important to guarantee the nutrient supply in the top 30 cm of the soil.
