This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizo...This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.展开更多
Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of lear...Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Methods Forty Sprague-Dawley rats （weighing approximately 200 g） were randomized into 5 groups （n = 8 in each group）： control group, model group, low-dose group （MK-801 0.5 mg/kg）, middle-dose group （MK-801 2 mg/kg）, and high-dose group （MK-801 10 mg/kg）. TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. Results The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase （nNOS）-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. Conclusion MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.展开更多
Objective：To investigate the silencing effects of recombinant adenovirus Ad-shRNA-MK on midkine（MK） gene in pancreatic cancer cells. Methods：Ad-shRNA-MK was used to infect pancreatic cancer BxPC-3 cells. Assays we...Objective：To investigate the silencing effects of recombinant adenovirus Ad-shRNA-MK on midkine（MK） gene in pancreatic cancer cells. Methods：Ad-shRNA-MK was used to infect pancreatic cancer BxPC-3 cells. Assays were conducted for knockdown of the MK gene on the day of infection and on the 1 ^st, 3^rd, 5^th, 7^th, and 9^th days post-infection by using immunocytochemistry, real-time RT-PCR, and Western blot analysis. Results：The adenoviral Ad-shRNA-PTN was constructed successfully, and infection was confirmed by electron microscopic observation. By using real-time RT-PCR, the inhibition rates of MK mRNA expression in the BxPC-3 cells were 20%, 80%, 55%, and 23% on the 1st, 3^th, 5^th, and 7^th days post-infection. Immunocytochemistry and Western blot analysis confirmed this effect at the gene product level. Conclusion：Efficient and specific knockdown of MK in pancreatic cancer cells by adenoviral Ad-shRNA-PTN is a potentially powerful tool for the study of gene therapy of pancreatic cancer nerve infiltration.展开更多
基金supported in parts by grants from the Hubei Province Key Technology R&D Program(No.2015BCE094)Wuhan Science and Technology Bureau Dawn Plan Project(No.201507040410216)+1 种基金Clinical Research Physician Program of Tongji Medical CollegeHUST and the Academic Frontier Youth Team Project of HUST
文摘This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.
基金supported by the grants from Nanjing Military Medical Science and Technology Innovation Project (No. 08MA007)
文摘Objective NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury （TBI）. The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Methods Forty Sprague-Dawley rats （weighing approximately 200 g） were randomized into 5 groups （n = 8 in each group）： control group, model group, low-dose group （MK-801 0.5 mg/kg）, middle-dose group （MK-801 2 mg/kg）, and high-dose group （MK-801 10 mg/kg）. TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. Results The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase （nNOS）-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. Conclusion MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.
文摘Objective：To investigate the silencing effects of recombinant adenovirus Ad-shRNA-MK on midkine（MK） gene in pancreatic cancer cells. Methods：Ad-shRNA-MK was used to infect pancreatic cancer BxPC-3 cells. Assays were conducted for knockdown of the MK gene on the day of infection and on the 1 ^st, 3^rd, 5^th, 7^th, and 9^th days post-infection by using immunocytochemistry, real-time RT-PCR, and Western blot analysis. Results：The adenoviral Ad-shRNA-PTN was constructed successfully, and infection was confirmed by electron microscopic observation. By using real-time RT-PCR, the inhibition rates of MK mRNA expression in the BxPC-3 cells were 20%, 80%, 55%, and 23% on the 1st, 3^th, 5^th, and 7^th days post-infection. Immunocytochemistry and Western blot analysis confirmed this effect at the gene product level. Conclusion：Efficient and specific knockdown of MK in pancreatic cancer cells by adenoviral Ad-shRNA-PTN is a potentially powerful tool for the study of gene therapy of pancreatic cancer nerve infiltration.
