The Experts below are selected from a list of 159099 Experts worldwide ranked by ideXlab platform
Howard C. Becker - One of the best experts on this subject based on the ideXlab platform.
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chronic ethanol exposure produces time and Brain Region dependent changes in gene coexpression networks
PLOS ONE, 2015Co-Authors: Elizabeth Osterndorffkahanek, Howard C. Becker, Marcelo F Lopez, Sean P Farris, Gayatri R Tiwari, Yury O Nunez, Adron R Harris, Dayne R MayfieldAbstract:Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and Brain Region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each Brain Region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each Region, there was little gene overlap across time (~20%). All Brain Regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each Brain Region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes.
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Brain Region-specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice
Addiction Biology, 2012Co-Authors: Roberto I Melendez, Jacqueline F Mcginty, Peter W. Kalivas, Howard C. BeckerAbstract:Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various Brain Regions. The present study investigated Brain Region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that Brain Region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal.
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Brain Region‐specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice
Addiction Biology, 2011Co-Authors: Roberto I Melendez, Jacqueline F Mcginty, Peter W. Kalivas, Howard C. BeckerAbstract:Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various Brain Regions. The present study investigated Brain Region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that Brain Region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal.
Xuyu Qian - One of the best experts on this subject based on the ideXlab platform.
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generation of human Brain Region specific organoids using a miniaturized spinning bioreactor
Nature Protocols, 2018Co-Authors: Xuyu Qian, Fadi Jacob, Mingxi Max Song, Ha Nam Nguyen, Hongjun Song, Guo Li MingAbstract:This protocol describes procedures for building the SpinΩ bioreactor for 3D tissue culture and differentiating human iPSCs into different Brain Region–specific organoids resembling developing human dorsal foreBrain, midBrain and hypothalamus. Human Brain organoids, 3D self-assembled neural tissues derived from pluripotent stem cells, are important tools for studying human Brain development and related disorders. Suspension cultures maintained by spinning bioreactors allow for the growth of large organoids despite the lack of vasculature, but commercially available spinning bioreactors are bulky in size and have low throughput. Here, we describe the procedures for building the miniaturized multiwell spinning bioreactor SpinΩ from 3D-printed parts and commercially available hardware. We also describe how to use SpinΩ to generate foreBrain, midBrain and hypothalamus organoids from human induced pluripotent stem cells (hiPSCs). These organoids recapitulate key dynamic features of the developing human Brain at the molecular, cellular and structural levels. The reduction in culture volume, increase in throughput and reproducibility achieved using our bioreactor and Region-specific differentiation protocols enable quantitative modeling of Brain disorders and compound testing. This protocol takes 14–84 d to complete (depending on the type of Brain Region–specific organoids and desired developmental stages), and organoids can be further maintained over 200 d. Competence with hiPSC culture is required for optimal results.
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Brain Region specific organoids using mini bioreactors for modeling zikv exposure
Cell, 2016Co-Authors: Xuyu Qian, Fadi Jacob, Ha Nam Nguyen, Mingxi M Song, Christopher Hadiono, Sarah C Ogden, Christy Hammack, Gregory R Hamersky, Chun Zhong, Ki Jun YoonAbstract:Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human Brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate foreBrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midBrain and hypothalamic organoids. Finally, we employed the foreBrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our Brain-Region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human Brain development and disease and for compound testing, including potential ZIKV antiviral drugs.
Michael F Miles - One of the best experts on this subject based on the ideXlab platform.
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ethanol responsive Brain Region expression networks implications for behavioral responses to acute ethanol in dba 2j versus c57bl 6j mice
The Journal of Neuroscience, 2005Co-Authors: Robnet T Kerns, Ajay Ravindranathan, Sajida Hassan, Mary P Cage, Tim York, James M Sikela, Robert W Williams, Michael F MilesAbstract:Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three Brain Regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanol-regulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal Regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was Brain Region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain Region-specific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving.
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Ethanol-Responsive Brain Region Expression Networks: Implications for Behavioral Responses to Acute Ethanol in DBA/2J versus C57BL/6J Mice
The Journal of Neuroscience, 2005Co-Authors: Robnet T Kerns, Ajay Ravindranathan, Sajida Hassan, Mary P Cage, Tim York, James M Sikela, Robert W Williams, Michael F MilesAbstract:Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three Brain Regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanol-regulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal Regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was Brain Region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain Region-specific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving.
Fadi Jacob - One of the best experts on this subject based on the ideXlab platform.
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generation of human Brain Region specific organoids using a miniaturized spinning bioreactor
Nature Protocols, 2018Co-Authors: Xuyu Qian, Fadi Jacob, Mingxi Max Song, Ha Nam Nguyen, Hongjun Song, Guo Li MingAbstract:This protocol describes procedures for building the SpinΩ bioreactor for 3D tissue culture and differentiating human iPSCs into different Brain Region–specific organoids resembling developing human dorsal foreBrain, midBrain and hypothalamus. Human Brain organoids, 3D self-assembled neural tissues derived from pluripotent stem cells, are important tools for studying human Brain development and related disorders. Suspension cultures maintained by spinning bioreactors allow for the growth of large organoids despite the lack of vasculature, but commercially available spinning bioreactors are bulky in size and have low throughput. Here, we describe the procedures for building the miniaturized multiwell spinning bioreactor SpinΩ from 3D-printed parts and commercially available hardware. We also describe how to use SpinΩ to generate foreBrain, midBrain and hypothalamus organoids from human induced pluripotent stem cells (hiPSCs). These organoids recapitulate key dynamic features of the developing human Brain at the molecular, cellular and structural levels. The reduction in culture volume, increase in throughput and reproducibility achieved using our bioreactor and Region-specific differentiation protocols enable quantitative modeling of Brain disorders and compound testing. This protocol takes 14–84 d to complete (depending on the type of Brain Region–specific organoids and desired developmental stages), and organoids can be further maintained over 200 d. Competence with hiPSC culture is required for optimal results.
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Brain Region specific organoids using mini bioreactors for modeling zikv exposure
Cell, 2016Co-Authors: Xuyu Qian, Fadi Jacob, Ha Nam Nguyen, Mingxi M Song, Christopher Hadiono, Sarah C Ogden, Christy Hammack, Gregory R Hamersky, Chun Zhong, Ki Jun YoonAbstract:Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human Brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate foreBrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midBrain and hypothalamic organoids. Finally, we employed the foreBrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our Brain-Region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human Brain development and disease and for compound testing, including potential ZIKV antiviral drugs.
Roberto I Melendez - One of the best experts on this subject based on the ideXlab platform.
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Brain Region-specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice
Addiction Biology, 2012Co-Authors: Roberto I Melendez, Jacqueline F Mcginty, Peter W. Kalivas, Howard C. BeckerAbstract:Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various Brain Regions. The present study investigated Brain Region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that Brain Region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal.
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Brain Region‐specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice
Addiction Biology, 2011Co-Authors: Roberto I Melendez, Jacqueline F Mcginty, Peter W. Kalivas, Howard C. BeckerAbstract:Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various Brain Regions. The present study investigated Brain Region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that Brain Region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal.
