Divergent effects of astroglial and microglial secretions on neuron growth and survival.

Brain glia have a secretory capacity which can modulate neuronal function. Astrocytes release proteins which enhance neuronal survival and induce neuronal growth and differentiation. These effects can be blocked by antagonists of voltage-dependent calcium channels and may be partly mimicked by Bay K 8644, a calcium channel agonist. Two of these neurotrophic proteins appear, on the basis of their physical properties and effects on ciliary ganglion neurons, to be ciliary neurotrophic factor and basic fibroblast growth factor. Activated microglia release a heat- and protease-stable neurotoxin of low molecular weight. This neurotoxicity is blocked by NMDA receptor antagonists. Ciliary neurons exposed to the microglial neurotoxin exhibit an abnormal distribution of neurofilament immunoreactivity, which becomes concentrated in a perinuclear region, while the astroglial growth factors induce neurofilament organization into an extensive neuritic network. The astrocyte-released growth factors can counteract the effect of the microglial neurotoxin and lead to unimpaired neural differentiation in the presence of the neurotoxin.