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Journal of Neuroscience, Vol 16, 2508-2521, Copyright © 1996 by Society for Neuroscience
Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function
S Elkabes, EM DiCicco-Bloom and IB Black
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway, New Jersey, 08854, USA.
Although microglia-mediated cytotoxicity has been extensively investigated,
little is known about the potential microglial role in neuronal and glial
support. Characterization of trophin elaboration by microglia and
identification of responsive populations may define novel functions. We now
report that microglia/brain macrophages express neurotrophins of the nerve
growth factor (NGF) gene family in vitro and in vivo, suggesting that these
cells promote development and normal function of neurons and glia.
Moreover, neurotrophins promote microglial proliferation and phagocytic
activity in vitro. We found that microglia express neurotrophins in a
region-specific manner and that within any region only subpopulations
elaborate trophins. Using an antiserum specific for neurotrophin-3 (NT-3)
with the microglial/macrophage marker OX-42 on postnatal day 10 in vivo,
double- labeled cells were identified in the cerebral cortex, globus
pallidus, and medulla; NT-3 was undetectable in OX-42-positive cells in the
ependyma, the external capsule, choroid plexus, and meninges. In contrast,
ramified microglia in the adult brain did not exhibit NT-3
immunoreactivity, suggesting developmental regulation of microglial NT- 3
expression. In situ hybridization studies on purified microglial cultures
confirmed that only subpopulations express the NGF and NT-3 genes,
substantiating the existence of microglial heterogeneity. We tentatively
conclude that microglial subtypes serve trophic roles in the normal brain,
in addition to exerting well documented deleterious actions in illness and
injury. Microglia were also responsive to neurotrophins: brain-derived
neurotrophic factor (BDNF) and NT-3 increased [3H]thymidine incorporation
in vitro, and NT-3 promoted proliferation. Moreover, NT-3 induced
phagocytic activity, suggesting that the factor plays a role in processes
associated with cellular activation.
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