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Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric o

Discussion in 'Mast Cell Disorders/Mastocytosis' started by nanonug, Oct 30, 2012.

  1. nanonug

    nanonug Senior Member

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    Virginia, USA
    J Neurochem. 1996 Mar;66(3):1157-66.
    Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway.

    Skaper SD, Facci L, Romanello S, Leon A.
    Source

    Researchlife S.c.p.A., Castelfranco Veneto (TV), Italy.
    Abstract

    Mast cells are pleiotropic bone marrow-derived cells found in mucosal and connective tissues and in close apposition to neurons, where they play important roles in tissue inflammation and in neuroimmune interactions. Connective tissue mast cells, with which intracranial mast cells share many characteristics, contain cytokines that can cause inflammation. Here, we report that myelin basic protein, a major suspected immunogen in multiple sclerosis, as well as an antigenic stimulus, provokes mast cells to trigger a delayed cytotoxicity for neurons in mixed neuron-gila cultures from hippocampus. Neurotoxicity required a prolonged period (12 h) of mast cell incubation, and appeared to depend largely on elaboration of the free radical nitric oxide by astrocytes. Activation of astrocytes was mediated, in part, by mast cell-secreted tumor necrosis factor-alpha. Myelin basic protein and 17 beta-estradiol had a synergistic action on the induction of mast cell-associated neuronal injury. The cognate mast cell line RBL-2H3, when subjected to an antigenic stimulus, released tumor necrosis factor-alpha which, together with exogenous interleukin-1 beta (or interferon-gamma), induced astroglia to produce neurotoxic quantities of nitric oxide. A small but significant proportion of mast cell-derived neurotoxicity under the above conditions occurred independently of glial nitric oxide synthase induction. Further, palmitoylethanolamide, which has been reported to reduce mast cell activation by a local autacoid mechanism, decreased neuron loss resulting from mast cell stimulation in the mixed cultures but not that caused by direct cytokine induction of astrocytic nitric oxide synthase. These results support the notion that brain mast cells could participate in the pathophysiology of chronic neurodegenerative and inflammatory diseases of the nervous system, and suggest that down-modulation of mast cell activation in such conditions could be of therapeutic benefit.
    PMID: 8769879
     
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  2. Marco

    Marco Old blackguard

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    Near Cognac, France
    Good find nanonug.

    I think you may be really onto something here.

    This is a good recent overview of the role of mast cells/glia in neuroinflammation:

    Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide


    Eggs for lunch for me :) :

    Interestingly PEA appears to depend on fully functioning mitochondria regulating PPARs for its anti-inflammatory effects.

    http://rstb.royalsocietypublishing.org/content/367/1607/3312.full

    This older paper also reports on the ability of palmitoylethanolamide to protect against glutamate excitotoxicity :

    http://www.pnas.org/content/93/9/3984.full.pdf
     
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