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Journal of Neuroscience, Vol 13, 29-37, Copyright © 1993 by Society for Neuroscience
Brain glia release factors with opposing actions upon neuronal survival
D Giulian, K Vaca and M Corpuz
Department of Neurology, Baylor College of Medicine, Houston, Texas 77031.
Microglia and astroglia have been thought to govern the survival of neurons
after damage to the CNS. To investigate these putative glia- neuron
relationships, we examined microglia and astroglia secretion products for
effects upon growth of cultured neurons. Activated microglia secrete small
neurotoxic factors (< 500 Da), while astroglia constitutively release
proteins (> 10 kDa) that promote neuronal growth. Proteins released from
astroglia, moreover, attenuate microglial toxicity, suggesting that
different glial populations have opposing actions upon neuronal survival.
Further study shows that neurotoxins from microglia are heat-stable,
protease-resistant molecules with biologic activities blocked by NMDA
receptor antagonists. Microglial factors, although toxic for chick ciliary
neurons and rat spinal cord neurons, did not reduce numbers of
oligodendroglia, astroglia, or Schwann cells in culture. The microglial
neurotoxins can be distinguished from cytokines, from free radical
intermediates, from the excitatory amino acids glutamate or aspartate, and
from the NMDA receptor-mediated toxin quinolinic acid. We propose that
secretion products from reactive microglia, but not astroglia, endanger
surviving neurons after CNS injury by release of a novel class of
neuron-killing molecules.
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