What Comes First Microglial Activation Or Neurodegeneration

Axotomy models have shown that neuronal death is not necessary to activate microglial cells.39 59 65 66 Conversely, they have also shown that microglial activation does not result in neuronal death, but instead coincides with neuron regeneration. A particularly fascinating aspect of the microglial response to axotomy of motoneurons is the rapid ensheathment of axotomized neurons by microglial cell processes. Not only does this result in "synaptic stripping,"59 but it also brings the microglial cell membrane into direct contact with the neuronal membrane. This is a situation which could clearly enhance any neuronal-microglial interactions, such as the transfer of neuronal injury signals, as well as any transfer of growth factors from microglia to neurons. At the same time, the ensheathment of axotomized neurons by microglial cell processes is very reminiscent of a phagocytic engulfment, and one could argue that if, in fact, a neuron was not going to recover from axotomy and was going to die, microglial cells would be situated perfectly to proceed with the removal of the dying cell. Thus, from a neuronal point of view, there may be a very fine line between receiving neurotrophic support and being eaten up, and any signals emitted from injured neurons should be sufficiently specific to enable this life or death decision. Since neurotoxicity is a well-documented property of cultured microglial cells,67-69 one wonders how and when microglial neurotoxicity comes to bear in vivo. Obviously, this dark side of the microglial cell must be under strict control in acute injury situations, since microglial activation in vivo does not result in additional neurodegeneration in the immediate vicinity. However, it is likely that some of this inhibition is lost in certain chronic conditions, such as Alzheimer's disease or HIV infection, and that in those circumstances the disinhibited microglia may indeed be the cause of neuronal damage.

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  • abela milano
    What comes first, microglial activation or neurodegeneration?
    1 month ago

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