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A Machado - One of the best experts on this subject based on the ideXlab platform.

  • lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal Dopaminergic System
    Journal of Neurochemistry, 2002
    Co-Authors: Angelica Castano, Antonio J Herrera, Josefina Cano, A Machado
    Abstract:

    The pathogenesis of Parkinson's disease is still poorly understood. To address the hypothesis that immune-mediated events, such as microglial activation, may be involved in the Dopaminergic neurodegeneration, we have studied the effect that intranigral injection of the immunostimulant lipopolysaccharide has on monoaminergic neurotransmitters in rats. Activation of microglial cells, visualized by immunohistochemistry with a specific monoclonal antibody, was already obvious 2 days after injection. In relation to the biochemical parameters studied, we found a significant decrease of dopamine levels in both the substantia nigra and striatum up to at least 21 days after intranigral injection of lipopolysaccharide. This result was supported by the decrease in tyrosine hydroxylase activity and the loss of tyrosine hydroxylase-positive neuronal bodies, shown by immunohistochemistry. These alterations of the Dopaminergic System did not reverse during the interval studied (21 days); conversely, the serotoninergic System suffered only transient damage. In addition, we found that the neurotoxic effect of lipopolysaccharide was not mediated by nitric oxide. Based on our results we suggest that the nigrostriatal Dopaminergic System is susceptible to damage by inflammatory events and that these may be implicated in neurodegeneration processes such as Parkinson's disease.

  • the single intranigral injection of lps as a new model for studying the selective effects of inflammatory reactions on Dopaminergic System
    Neurobiology of Disease, 2000
    Co-Authors: Antonio J Herrera, Angelica Castano, Jose L Venero, Josefina Cano, A Machado
    Abstract:

    We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease (PD). LPS induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a characteristic clustering of macrophage cells around blood-vessels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the Dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neurons. The damage to the DA neurons in the SN was permanent, as observed 1 year postinjection. Unlike the direct death of Dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to cause indirect death due to inflammatory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective effects of inflammatory reaction on Dopaminergic System and also potentially useful for studying PD.

Angelica Castano - One of the best experts on this subject based on the ideXlab platform.

  • lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal Dopaminergic System
    Journal of Neurochemistry, 2002
    Co-Authors: Angelica Castano, Antonio J Herrera, Josefina Cano, A Machado
    Abstract:

    The pathogenesis of Parkinson's disease is still poorly understood. To address the hypothesis that immune-mediated events, such as microglial activation, may be involved in the Dopaminergic neurodegeneration, we have studied the effect that intranigral injection of the immunostimulant lipopolysaccharide has on monoaminergic neurotransmitters in rats. Activation of microglial cells, visualized by immunohistochemistry with a specific monoclonal antibody, was already obvious 2 days after injection. In relation to the biochemical parameters studied, we found a significant decrease of dopamine levels in both the substantia nigra and striatum up to at least 21 days after intranigral injection of lipopolysaccharide. This result was supported by the decrease in tyrosine hydroxylase activity and the loss of tyrosine hydroxylase-positive neuronal bodies, shown by immunohistochemistry. These alterations of the Dopaminergic System did not reverse during the interval studied (21 days); conversely, the serotoninergic System suffered only transient damage. In addition, we found that the neurotoxic effect of lipopolysaccharide was not mediated by nitric oxide. Based on our results we suggest that the nigrostriatal Dopaminergic System is susceptible to damage by inflammatory events and that these may be implicated in neurodegeneration processes such as Parkinson's disease.

  • the single intranigral injection of lps as a new model for studying the selective effects of inflammatory reactions on Dopaminergic System
    Neurobiology of Disease, 2000
    Co-Authors: Antonio J Herrera, Angelica Castano, Jose L Venero, Josefina Cano, A Machado
    Abstract:

    We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease (PD). LPS induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a characteristic clustering of macrophage cells around blood-vessels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the Dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neurons. The damage to the DA neurons in the SN was permanent, as observed 1 year postinjection. Unlike the direct death of Dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to cause indirect death due to inflammatory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective effects of inflammatory reaction on Dopaminergic System and also potentially useful for studying PD.

Antonio J Herrera - One of the best experts on this subject based on the ideXlab platform.

  • lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal Dopaminergic System
    Journal of Neurochemistry, 2002
    Co-Authors: Angelica Castano, Antonio J Herrera, Josefina Cano, A Machado
    Abstract:

    The pathogenesis of Parkinson's disease is still poorly understood. To address the hypothesis that immune-mediated events, such as microglial activation, may be involved in the Dopaminergic neurodegeneration, we have studied the effect that intranigral injection of the immunostimulant lipopolysaccharide has on monoaminergic neurotransmitters in rats. Activation of microglial cells, visualized by immunohistochemistry with a specific monoclonal antibody, was already obvious 2 days after injection. In relation to the biochemical parameters studied, we found a significant decrease of dopamine levels in both the substantia nigra and striatum up to at least 21 days after intranigral injection of lipopolysaccharide. This result was supported by the decrease in tyrosine hydroxylase activity and the loss of tyrosine hydroxylase-positive neuronal bodies, shown by immunohistochemistry. These alterations of the Dopaminergic System did not reverse during the interval studied (21 days); conversely, the serotoninergic System suffered only transient damage. In addition, we found that the neurotoxic effect of lipopolysaccharide was not mediated by nitric oxide. Based on our results we suggest that the nigrostriatal Dopaminergic System is susceptible to damage by inflammatory events and that these may be implicated in neurodegeneration processes such as Parkinson's disease.

  • the single intranigral injection of lps as a new model for studying the selective effects of inflammatory reactions on Dopaminergic System
    Neurobiology of Disease, 2000
    Co-Authors: Antonio J Herrera, Angelica Castano, Jose L Venero, Josefina Cano, A Machado
    Abstract:

    We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease (PD). LPS induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a characteristic clustering of macrophage cells around blood-vessels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the Dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neurons. The damage to the DA neurons in the SN was permanent, as observed 1 year postinjection. Unlike the direct death of Dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to cause indirect death due to inflammatory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective effects of inflammatory reaction on Dopaminergic System and also potentially useful for studying PD.

Bernd Neumaier - One of the best experts on this subject based on the ideXlab platform.

  • dnmt3a2 dnmt3l overexpression in the Dopaminergic System of mice increases exercise behavior through signaling changes in the hypothalamus
    International Journal of Molecular Sciences, 2020
    Co-Authors: Di Cui, Andrea Mesaros, Gregor Burdeos, Ingo Voigt, Patrick Giavalisco, Yvonne Hinze, Martin Purrio, Bernd Neumaier
    Abstract:

    Dnmt3a2, a de novo DNA methyltransferase, is induced by neuronal activity and participates in long-term memory formation with the increased expression of synaptic plasticity genes. We wanted to determine if Dnmt3a2 with its partner Dnmt3L may influence motor behavior via the Dopaminergic System. To this end, we generated a mouse line, Dnmt3a2/3LDat/wt, with dopamine transporter (DAT) promotor driven Dnmt3a2/3L overexpression. The mice were studied with behavioral paradigms (e.g., cylinder test, open field, and treadmill), brain slice patch clamp recordings, ex vivo metabolite analysis, and in vivo positron emission tomography (PET) using the Dopaminergic tracer 6-[18F]FMT. The results showed that spontaneous activity and exercise performance were enhanced in Dnmt3a2/3LDat/wt mice compared to Dnmt3a2/3Lwt/wt controls. Dopaminergic substantia nigra pars compacta neurons of Dnmt3a2/3LDat/wt animals displayed a higher fire frequency and excitability. However, dopamine concentration was not increased in the striatum, and dopamine metabolite concentration was even significantly decreased. Striatal 6-[18F]FMT uptake, reflecting aromatic L-amino acid decarboxylase activity, was the same in Dnmt3a2/3LDat/wt mice and controls. [18F]FDG PET showed that hypothalamic metabolic activity was tightly linked to motor behavior in Dnmt3a2/3LDat/wt mice. Furthermore, dopamine biosynthesis and motor-related metabolic activity were correlated in the hypothalamus. Our findings suggest that Dnmt3a2/3L, when overexpressed in Dopaminergic neurons, modulates motor performance via activation of the nigrostriatal pathway. This does not involve increased dopamine synthesis.

Josefina Cano - One of the best experts on this subject based on the ideXlab platform.

  • lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal Dopaminergic System
    Journal of Neurochemistry, 2002
    Co-Authors: Angelica Castano, Antonio J Herrera, Josefina Cano, A Machado
    Abstract:

    The pathogenesis of Parkinson's disease is still poorly understood. To address the hypothesis that immune-mediated events, such as microglial activation, may be involved in the Dopaminergic neurodegeneration, we have studied the effect that intranigral injection of the immunostimulant lipopolysaccharide has on monoaminergic neurotransmitters in rats. Activation of microglial cells, visualized by immunohistochemistry with a specific monoclonal antibody, was already obvious 2 days after injection. In relation to the biochemical parameters studied, we found a significant decrease of dopamine levels in both the substantia nigra and striatum up to at least 21 days after intranigral injection of lipopolysaccharide. This result was supported by the decrease in tyrosine hydroxylase activity and the loss of tyrosine hydroxylase-positive neuronal bodies, shown by immunohistochemistry. These alterations of the Dopaminergic System did not reverse during the interval studied (21 days); conversely, the serotoninergic System suffered only transient damage. In addition, we found that the neurotoxic effect of lipopolysaccharide was not mediated by nitric oxide. Based on our results we suggest that the nigrostriatal Dopaminergic System is susceptible to damage by inflammatory events and that these may be implicated in neurodegeneration processes such as Parkinson's disease.

  • the single intranigral injection of lps as a new model for studying the selective effects of inflammatory reactions on Dopaminergic System
    Neurobiology of Disease, 2000
    Co-Authors: Antonio J Herrera, Angelica Castano, Jose L Venero, Josefina Cano, A Machado
    Abstract:

    We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease (PD). LPS induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a characteristic clustering of macrophage cells around blood-vessels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the Dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neurons. The damage to the DA neurons in the SN was permanent, as observed 1 year postinjection. Unlike the direct death of Dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to cause indirect death due to inflammatory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective effects of inflammatory reaction on Dopaminergic System and also potentially useful for studying PD.