Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injec...Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin (p38) mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.展开更多
Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carr...Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyI-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyI-D-aspartate receptors.展开更多
Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current(INMDA) in cortical neurons, and protect neurons. In this s...Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current(INMDA) in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.展开更多
High-throughput genotyping chips have produced huge datasets for genome-wide association studies (GWAS) that have contributed greatly to discovering susceptibility genes for complex diseases. There are two strategie...High-throughput genotyping chips have produced huge datasets for genome-wide association studies (GWAS) that have contributed greatly to discovering susceptibility genes for complex diseases. There are two strategies for performing data analysis for GWAS. One strategy is to use open-source or commercial packages that are designed for GWAS. The other is to take advantage of classic genetic programs with specific functions, such as linkage disequilibrium mapping, haplotype inference and transmission disequilibrium tests. However, most classic programs that are available are not suitable for analyzing chip data directly and require custom-made input, which results in the inconvenience of converting raw genotyping files into various data formats. We developed a powerful, user-friendly, lightweight program named SNPTransformer for GWAS that includes five major modules (Transformer, Operator, Previewer, Coder and Simulator). The toolkit not only works for transforming the genotyping files into ten input formats for use with classic genetics packages, but also carries out useful functions such as relational operations on IDs, previewing data files, recoding data formats and simulating marker files, among other functions. It bridges upstream raw genotyping data with downstream genetic programs, and can act as an in-hand toolkit for human geneticists, especially for non-programmers. SNPTransformer is freely available at http://snptransformer.sourceforge.net.展开更多
文摘Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin (p38) mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.
文摘Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyI-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyI-D-aspartate receptors.
文摘Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current(INMDA) in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.
基金supported by Zhejiang Provincial Natural Science Foundation (No. Y2100240)Ningbo Natural Science Foundation (No. 2009A610142)+1 种基金Zhejiang Provincial Health Department Foundation (No. 2009A183)the Hulan Scholar Fund and the K.C. Wong Magna Fund at Ningbo University
文摘High-throughput genotyping chips have produced huge datasets for genome-wide association studies (GWAS) that have contributed greatly to discovering susceptibility genes for complex diseases. There are two strategies for performing data analysis for GWAS. One strategy is to use open-source or commercial packages that are designed for GWAS. The other is to take advantage of classic genetic programs with specific functions, such as linkage disequilibrium mapping, haplotype inference and transmission disequilibrium tests. However, most classic programs that are available are not suitable for analyzing chip data directly and require custom-made input, which results in the inconvenience of converting raw genotyping files into various data formats. We developed a powerful, user-friendly, lightweight program named SNPTransformer for GWAS that includes five major modules (Transformer, Operator, Previewer, Coder and Simulator). The toolkit not only works for transforming the genotyping files into ten input formats for use with classic genetics packages, but also carries out useful functions such as relational operations on IDs, previewing data files, recoding data formats and simulating marker files, among other functions. It bridges upstream raw genotyping data with downstream genetic programs, and can act as an in-hand toolkit for human geneticists, especially for non-programmers. SNPTransformer is freely available at http://snptransformer.sourceforge.net.