Cellular basis of inflammation in the enteric nervous system

Abstract

There is limited knowledge of immunocyte-myenteric neuronal interaction and the role of iNOS in myenteric neuronal injury. This research sought to examine the role of macrophages, NO, and iNOS inhibitors in myenteric neurodegeneration. Increased NO synthesis in macrophages and its effects on myenteric neurons were investigated in cell cultures. Using rodent models of inflammation, we further examined NO-dependent neurotoxicity. In the presence of activated macrophages neuronal injury and degeneration occurred; however the myenteric neurons showed greater resistance to oxidative challenge than cortical neurons. Pretreatment with iNOS inhibitors significantly reduced these inflammatory effects. Myenteric neuronal injury was also evident in experimental colitis, and iNOS selective inhibitor protected the myenteric neurons from inflammation and degeneration. In conclusion, these results show that activated macrophage-derived NO is important in inflammation-dependent myenteric neurodegeneration, and iNOS inhibitors can protect myenteric neurons from degeneration. Two potential strategies for neuroprotection in gut inflammation are defined.