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The Journal of Neuroscience, March 1, 1999, 19(5):1708-1716
Activated Macrophages and Microglia Induce Dopaminergic Sprouting
in the Injured Striatum and Express Brain-Derived Neurotrophic Factor
and Glial Cell Line-Derived Neurotrophic Factor
Peter E.
Batchelor,
Gabriel T.
Liberatore,
John Y. F.
Wong,
Michelle J.
Porritt,
Fenneke
Frerichs,
Geoffrey A.
Donnan, and
David W. Howells
Departments of Medicine and Neurology, University of Melbourne,
Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia
Nigrostriatal dopaminergic neurons undergo sprouting around the
margins of a striatal wound. The mechanism of this periwound sprouting
has been unclear. In this study, we have examined the role played by
the macrophage and microglial response that follows striatal injury.
Macrophages and activated microglia quickly accumulate after injury and
reach their greatest numbers in the first week. Subsequently, the
number of both cell types declines rapidly in the first month and
thereafter more slowly. Macrophage numbers eventually cease to decline,
and a sizable group of these cells remains at the wound site and forms
a long-term, highly activated resident population. This population of
macrophages expresses increasing amounts of glial cell line-derived
neurotrophic factor mRNA with time. Brain-derived neurotrophic factor
mRNA is also expressed in and around the wound site. Production of this
factor is by both activated microglia and, to a lesser extent,
macrophages. The production of these potent dopaminergic neurotrophic
factors occurs in a similar spatial distribution to sprouting
dopaminergic fibers. Moreover, dopamine transporter-positive
dopaminergic neurites can be seen growing toward and embracing
hemosiderin-filled wound macrophages. The dopaminergic sprouting that
accompanies striatal injury thus appears to result from neurotrophic
factor secretion by activated macrophages and microglia at the wound site.
Key words:
sprouting; BDNF; GDNF; macrophage; microglia; dopamine; striatal injury
Copyright © 1999 Society for Neuroscience 0270-6474/99/1951708-09$05.00/0
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