The Experts below are selected from a list of 2052 Experts worldwide ranked by ideXlab platform

Sarah F Leibowitz - One of the best experts on this subject based on the ideXlab platform.

  • third ventricular injection of ccl2 in rat embryo stimulates ccl2 ccr2 Neuroimmune System in neuroepithelial radial glia progenitor cells relation to sexually dimorphic stimulatory effects on peptide neurons in lateral hypothalamus
    Neuroscience, 2020
    Co-Authors: Guoqing Chang, Olga Karatayev, Devi Sai Sri Kavya Boorgu, Sarah F Leibowitz
    Abstract:

    Abstract Clinical and animal studies show maternal alcohol consumption during pregnancy causes in offspring persistent alterations in Neuroimmune and neurochemical Systems known to increase alcohol drinking and related behaviors. Studies in lateral hypothalamus (LH) demonstrate in adolescent offspring that maternal oral administration of ethanol stimulates the neuropeptide, melanin-concentrating hormone (MCH), together with the inflammatory chemokine C–C motif ligand 2 (CCL2) and its receptor CCR2 which are increased in most MCH neurons. These effects, consistently stronger in females than males, are detected in embryos, not only in LH but hypothalamic neuroepithelium (NEP) along the third ventricle where neurons are born and CCL2 is stimulated within radial glia progenitor cells and their laterally projecting processes that facilitate MCH neuronal migration toward LH. With ethanol’s effects similarly produced by maternal peripheral CCL2 administration and blocked by CCR2 antagonist, we tested here using in utero intracerebroventricular (ICV) injections whether CCL2 acts locally within the embryonic NEP. After ICV injection of CCL2 (0.1 µg/µl) on embryonic day 14 (E14) when neurogenesis peaks, we observed in embryos just before birth (E19) a significant increase in endogenous CCL2 within radial glia cells and their processes in NEP. These auto-regulatory effects, evident only in female embryos, were accompanied by increased density of CCL2 and MCH neurons in LH, more strongly in females than males. These results support involvement of embryonic CCL2/CCR2 Neuroimmune System in radial glia progenitor cells in mediating sexually dimorphic effects of maternal challenges such as ethanol on LH MCH neurons that colocalize CCL2 and CCR2.

  • ccl2 ccr2 chemokine System in embryonic hypothalamus involvement in sexually dimorphic stimulatory effects of prenatal ethanol exposure on peptide expressing neurons
    Neuroscience, 2020
    Co-Authors: Guoqing Chang, Olga Karatayev, Devi Sai Sri Kavya Boorgu, Sarah F Leibowitz
    Abstract:

    Abstract Maternal consumption of ethanol during pregnancy is known to increase the offspring’s risk for developing alcohol use disorders and associated behavioral disturbances. Studies in adolescent and adult animals suggest the involvement of Neuroimmune and neurochemical Systems in the brain that control these behaviors. To understand the origin of these effects during early developmental stages, we examined in the embryo and neonate the effects of maternal intraoral administration of ethanol (2 g/kg/day) from embryonic day 10 (E10) to E15 on the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 in a specific, dense population of neurons in the lateral hypothalamus (LH), where they are closely related to an orexigenic neuropeptide, melanin-concentrating hormone (MCH), known to promote ethanol consumption and related behaviors. We found that prenatal ethanol exposure increases the expression and density of CCL2 and CCR2 cells along with MCH neurons in the LH and the colocalization of CCL2 with MCH. We also discovered that these effects are sexually dimorphic, consistently stronger in female embryos, and are blocked by maternal administration of a CCL2 antibody (1 and 5 µg/day, i.p., E10-E15) that neutralizes endogenous CCL2 and of a CCR2 antagonist INCB3344 (1 mg/day, i.p., E10-E15) that blocks CCL2′s main receptor. These results, which in the embryo anatomically and functionally link the CCL2/CCR2 System to MCH neurons in the LH, suggest an important role for this Neuroimmune System in mediating ethanol’s sexually dimorphic, stimulatory effect on MCH neurons that may promote higher level of alcohol consumption described in females.

David G Ashbrook - One of the best experts on this subject based on the ideXlab platform.

  • epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice a model of gulf war illness
    Journal of Neuroinflammation, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick
    Abstract:

    Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments.

  • Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness
    BMC, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick, James P. O’callaghan, Patrick O. Mcgowan
    Abstract:

    Abstract Background Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. Methods C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. Results We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Conclusions Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments

Guoqing Chang - One of the best experts on this subject based on the ideXlab platform.

  • third ventricular injection of ccl2 in rat embryo stimulates ccl2 ccr2 Neuroimmune System in neuroepithelial radial glia progenitor cells relation to sexually dimorphic stimulatory effects on peptide neurons in lateral hypothalamus
    Neuroscience, 2020
    Co-Authors: Guoqing Chang, Olga Karatayev, Devi Sai Sri Kavya Boorgu, Sarah F Leibowitz
    Abstract:

    Abstract Clinical and animal studies show maternal alcohol consumption during pregnancy causes in offspring persistent alterations in Neuroimmune and neurochemical Systems known to increase alcohol drinking and related behaviors. Studies in lateral hypothalamus (LH) demonstrate in adolescent offspring that maternal oral administration of ethanol stimulates the neuropeptide, melanin-concentrating hormone (MCH), together with the inflammatory chemokine C–C motif ligand 2 (CCL2) and its receptor CCR2 which are increased in most MCH neurons. These effects, consistently stronger in females than males, are detected in embryos, not only in LH but hypothalamic neuroepithelium (NEP) along the third ventricle where neurons are born and CCL2 is stimulated within radial glia progenitor cells and their laterally projecting processes that facilitate MCH neuronal migration toward LH. With ethanol’s effects similarly produced by maternal peripheral CCL2 administration and blocked by CCR2 antagonist, we tested here using in utero intracerebroventricular (ICV) injections whether CCL2 acts locally within the embryonic NEP. After ICV injection of CCL2 (0.1 µg/µl) on embryonic day 14 (E14) when neurogenesis peaks, we observed in embryos just before birth (E19) a significant increase in endogenous CCL2 within radial glia cells and their processes in NEP. These auto-regulatory effects, evident only in female embryos, were accompanied by increased density of CCL2 and MCH neurons in LH, more strongly in females than males. These results support involvement of embryonic CCL2/CCR2 Neuroimmune System in radial glia progenitor cells in mediating sexually dimorphic effects of maternal challenges such as ethanol on LH MCH neurons that colocalize CCL2 and CCR2.

  • ccl2 ccr2 chemokine System in embryonic hypothalamus involvement in sexually dimorphic stimulatory effects of prenatal ethanol exposure on peptide expressing neurons
    Neuroscience, 2020
    Co-Authors: Guoqing Chang, Olga Karatayev, Devi Sai Sri Kavya Boorgu, Sarah F Leibowitz
    Abstract:

    Abstract Maternal consumption of ethanol during pregnancy is known to increase the offspring’s risk for developing alcohol use disorders and associated behavioral disturbances. Studies in adolescent and adult animals suggest the involvement of Neuroimmune and neurochemical Systems in the brain that control these behaviors. To understand the origin of these effects during early developmental stages, we examined in the embryo and neonate the effects of maternal intraoral administration of ethanol (2 g/kg/day) from embryonic day 10 (E10) to E15 on the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 in a specific, dense population of neurons in the lateral hypothalamus (LH), where they are closely related to an orexigenic neuropeptide, melanin-concentrating hormone (MCH), known to promote ethanol consumption and related behaviors. We found that prenatal ethanol exposure increases the expression and density of CCL2 and CCR2 cells along with MCH neurons in the LH and the colocalization of CCL2 with MCH. We also discovered that these effects are sexually dimorphic, consistently stronger in female embryos, and are blocked by maternal administration of a CCL2 antibody (1 and 5 µg/day, i.p., E10-E15) that neutralizes endogenous CCL2 and of a CCR2 antagonist INCB3344 (1 mg/day, i.p., E10-E15) that blocks CCL2′s main receptor. These results, which in the embryo anatomically and functionally link the CCL2/CCR2 System to MCH neurons in the LH, suggest an important role for this Neuroimmune System in mediating ethanol’s sexually dimorphic, stimulatory effect on MCH neurons that may promote higher level of alcohol consumption described in females.

Gordon Broderick - One of the best experts on this subject based on the ideXlab platform.

  • epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice a model of gulf war illness
    Journal of Neuroinflammation, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick
    Abstract:

    Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments.

  • Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness
    BMC, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick, James P. O’callaghan, Patrick O. Mcgowan
    Abstract:

    Abstract Background Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. Methods C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. Results We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Conclusions Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments

Benjamin Hing - One of the best experts on this subject based on the ideXlab platform.

  • epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice a model of gulf war illness
    Journal of Neuroinflammation, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick
    Abstract:

    Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments.

  • Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness
    BMC, 2018
    Co-Authors: David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C De Vega, Diane B Miller, Gordon Broderick, James P. O’callaghan, Patrick O. Mcgowan
    Abstract:

    Abstract Background Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and Neuroimmune and neuroinflammatory components. An estimated 25–32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the Neuroimmune System. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. Methods C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. Results We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal System, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. Conclusions Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments