Axon degeneration is a hallmark of several central nervous system (CNS) disorders, including multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Previous neuroprotective approaches have mainly focused on reversal or prevention of neuronal cell body degeneration or death. However, experimental evidence suggests that mechanisms of axon degeneration may differ from cell death mechanisms, and that therapeutic agents that protect cell bodies may not protect axons. Moreover, axon degeneration underlies neurologic disability and may, in some cases, represent an important initial step that leads to neuronal death. Here, we develop a novel quantitative microfluidic-based methodology to assess mechanisms of axon degeneration caused by local neuroinflammation. We find that LPS-stimulated microglia release soluble factors that, when applied locally to axons, result in axon degeneration. This local axon degeneration is mediated by microglial MyD88/p38 MAPK signaling and concomitant production of nitric oxide (NO). Intra-axonal mechanisms of degeneration involve JNK phosphorylation. Curcumin, a compound with both anti-oxidant and JNK inhibitory properties, specifically protects axons, but not neuronal cell bodies, from NO-mediated degeneration. Overall, our platform provides mechanistic insights into local axon degeneration, identifies curcumin as a novel axon protectant in the setting of neuroinflammation, and allows for ready screening of axon protective drugs.
This local axon degeneration is mediated by microglial MyD88/p38 MAPK signaling and concomitant production of nitric oxide (NO).
ThisIsMA wrote:I see that kind of sentence a lot: that "X" is mediated by "Y". Can you explain what that means? Its the word "mediated" that's tripping me up. I know what the word means in other contexts but it just occurred to me I might be misunderstanding it in a medical study context.
In the above quoted sentence are they saying that increased production of nitric oxide reduces the rate of axon degeneration, or does it make it worse?
M.A. (<--trying to improve my study reading skills)!
Not to answer for Cheer, but I think 'caused by' is likely the correct interpretation.
To resolve or settle (differences) by working with all the conflicting parties
to cause a change, as in stimulation by a hormone.
the nitric oxide production is bad, causing the axon degeneration!?This local axon degeneration is mediated by microglial MyD88/p38 MAPK signaling and concomitant production of nitric oxide (NO).
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