Identity of neurotrophic molecules released from astroglia by vasoactive intestinal peptide.

Subnanomolar concentrations of VIP elicit a survival-producing action in CNS cultures composed of both astroglia and neurons. This neurotrophic action is mediated by a complex array of substances released by VIP from astrocytes. Included in this glial protein mixture is a cytokine (interleukin-1 alpha), a serine protease inhibitor (protease nexin I), and an extracellular stress protein (activity-dependent neurotrophic factor). In dissociated spinal cord cultures, all of these substances exhibit neuroprotection from neuronal cell death produced by electrical blockade with tetrodotoxin. All these substances produce neuronal cell death when test cultures are treated with neutralizing antisera to any one of them. They are all apparently necessary for the survival of a subpopulation of neurons that are dependent on spontaneous, excitatory neurotransmission. Our view is that these substances are components of a glia-derived environment that regulates, together with target-derived growth factors, the survival fate of developing neurons. In addition, it is our belief that some of these glia-derived substances will be found to have active roles in the injury response to the CNS or in the regulation of VIP-mediated growth in other tissues. Drugs based on these substances may provide therapeutic agents for the treatment of neurodegeneration and tumor growth.