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Cellular dynamics underlying regeneration of damaged axons differs from initial axon development


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Blizzard, CA, Haas, MA, Vickers, JC and Dickson, TC 2007 , 'Cellular dynamics underlying regeneration of damaged axons differs from initial axon development' , European Journal of Neuroscience, vol. 26, no. 5 , pp. 1100-1108 , doi: 10.1111/j.1460-9568.2007.057.

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While long-distance regeneration may be limited in mammalian species, it is becoming apparent that damaged mature neurons retain
some capacity for attempted regeneration and that the adult CNS is not entirely inhibitory to axon growth. Our investigations show
that there are critical intrinsic features of postinjury axonal regeneration that differ from initial axon development, and that these
distinct differences may account for the limited and inappropriate regenerative response that currently characterizes the mature CNS.
We compared the neurochemical and dynamic characteristics of developing axons to relatively mature regenerating axons, utilizing
an in vitro model of axonal transection to long-term cultured rat cortical neurons. Immunolabelling studies revealed that regenerating
and developing axons have a similar localization of cytoskeletal proteins, but the tips of regenerating axons, although morphologically
similar, were smaller with reduced fillopodial extension, relative to developmental growth cones. Live imaging demonstrated that
regenerating axons exhibited significantly less outgrowth than developmental neurites. Furthermore, growth cones of regenerating
axons had a significant reduction in pausing, considered vital for interstitial branching and pathfinding, than did developmental growth
cones. In addition, unlike developing axons, the regenerating axons were unresponsive to the growth factors BDNF and GDNF. Thus,
although similar in their cytoskeletal composition, the growth cones of regenerative sprouts differed from their developmental
counterparts in their size, their dynamic behaviour and their ability to respond to critical growth factors. These intrinsic differences
may account for the inability of post-traumatic locally sprouting axons to make accurate pathway decisions and successfully respond
to trauma.

Item Type: Article
Authors/Creators:Blizzard, CA and Haas, MA and Vickers, JC and Dickson, TC
Journal or Publication Title: European Journal of Neuroscience
ISSN: 1460-9568
DOI / ID Number: 10.1111/j.1460-9568.2007.057
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