Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(N...Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.展开更多
The early history of Earth is poorly understood,due to the lack of ancient rocks formed after the formation of the newborn Earth,especiallyfor thefirst 500 million years(Hadean Eon).To our knowledge,this period is the...The early history of Earth is poorly understood,due to the lack of ancient rocks formed after the formation of the newborn Earth,especiallyfor thefirst 500 million years(Hadean Eon).To our knowledge,this period is the most geodynamically vigorous in the crustal evolution history of Earth[1],and is characterized by intense collision with meteorites and the formation of a global magma ocean(~4.41 Ga;cf.review article by Ref.[2]).展开更多
Cerium is one of multivalent rear earth elements, which can transfer from trivalence to tretavalence at oxidizing environment. This process may cause variable degrees of fractionation of Ce from other trivalent rear e...Cerium is one of multivalent rear earth elements, which can transfer from trivalence to tretavalence at oxidizing environment. This process may cause variable degrees of fractionation of Ce from other trivalent rear earth elements, and thus may provide specific insight into the geological processes associated with marked redoxomorphism. Multiple geochemical tracing of Sr-Nd-Ce isotopes are performed on the felsic and mafic intrusives of the Neoproterozoic(~800 Ma) Huangling complex located at the eastern Three Gorges, South China. The intrusive rocks exclusively show various extents of negative Ce anomalies. On the εCe-εNd plot, most samples from the mafic intrusions scatter within the second quadrant, whereas those from the felsic intrusions within the fourth Quadrant. Both of the two groups exhibit relatively large range of ?Ce(t) variation but limited ?Nd(t) range, which cause a deviation from the "crustal array" and reveal a decoupled Nd-Ce isotope correlation. The intermediate-felsic suite have varied Ce/Ce* ratios but broadly proximate εCe(t) values, indicating that their negative Ce anomalies were generated during the magmatism; on the contrary, a positive correlation between εCe(t) and Ce/Ce* is observed for the intermediate-mafic suite, an indication of an origin of post-magmatic alteration or metamorphism for their Ce anomalies. Calculation of model age, the occurrence age of negative Ce anomalies(TCe) for the intermediate-mafic samples infers that the alteration events took place 〉350 Ma. Data showed that negative Ce anomalies of the felsic intrusions may reflect an increase of oxygen fugacity during magma ascending, rather than an inheritance from their source rocks. This explanation implies that the Neoproterozoic magmatism occurred at the continental nucleus of the Yangtze block were developing at a geodynamic context of rapidly regional uplifting.展开更多
基金supported by the National Natural Science Foundation of China(81872654,81703264)Fundamental Research Funds of Shandong University(2016JC020),ChinaNatural Science Foundation of Shandong Province(ZR2017MH002),China
文摘Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and cortex.Mechanistically, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.
基金supported by the Chinese Postdoctoral Science Foundation (2022M710876)the Natural Science Foundation of Anhui Province (2108085MD133)+1 种基金the China Geological Survey (DD20190154 and DD20221689)the PI Project of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (GML2020GD0802)。
文摘The early history of Earth is poorly understood,due to the lack of ancient rocks formed after the formation of the newborn Earth,especiallyfor thefirst 500 million years(Hadean Eon).To our knowledge,this period is the most geodynamically vigorous in the crustal evolution history of Earth[1],and is characterized by intense collision with meteorites and the formation of a global magma ocean(~4.41 Ga;cf.review article by Ref.[2]).
基金supported by the National Natural Science Foundation of China (Nos. 41373037, 41173048, 41503025)
文摘Cerium is one of multivalent rear earth elements, which can transfer from trivalence to tretavalence at oxidizing environment. This process may cause variable degrees of fractionation of Ce from other trivalent rear earth elements, and thus may provide specific insight into the geological processes associated with marked redoxomorphism. Multiple geochemical tracing of Sr-Nd-Ce isotopes are performed on the felsic and mafic intrusives of the Neoproterozoic(~800 Ma) Huangling complex located at the eastern Three Gorges, South China. The intrusive rocks exclusively show various extents of negative Ce anomalies. On the εCe-εNd plot, most samples from the mafic intrusions scatter within the second quadrant, whereas those from the felsic intrusions within the fourth Quadrant. Both of the two groups exhibit relatively large range of ?Ce(t) variation but limited ?Nd(t) range, which cause a deviation from the "crustal array" and reveal a decoupled Nd-Ce isotope correlation. The intermediate-felsic suite have varied Ce/Ce* ratios but broadly proximate εCe(t) values, indicating that their negative Ce anomalies were generated during the magmatism; on the contrary, a positive correlation between εCe(t) and Ce/Ce* is observed for the intermediate-mafic suite, an indication of an origin of post-magmatic alteration or metamorphism for their Ce anomalies. Calculation of model age, the occurrence age of negative Ce anomalies(TCe) for the intermediate-mafic samples infers that the alteration events took place 〉350 Ma. Data showed that negative Ce anomalies of the felsic intrusions may reflect an increase of oxygen fugacity during magma ascending, rather than an inheritance from their source rocks. This explanation implies that the Neoproterozoic magmatism occurred at the continental nucleus of the Yangtze block were developing at a geodynamic context of rapidly regional uplifting.