ASTROGLIA NEURON INTERACTIONS THAT PROMOTE LONG-TERM NEURONAL SURVIVAL

Besides intrinsic determinants of cell growth, epigenetic signals have been proposed to regulate development and maintenance of neurons. Her e we provide evidence that cerebral astrocytes contribute significantl y to the set of environmental influences that are required for long-te rm survival of neurons derived from the mammalian central nervous syst em. Cerebral astrocytes in serum-free culture express diffusible and n on-diffusible neuron-supporting signals, including cell-adhesive neuri te growth-promoting glycoproteins, diffusible neurotrophic factors as well as membrane-bound molecules that mediate cell contact interaction s. The combination and synergistic interaction of these environmental signals markedly enhance the survival of brain neurons. While astrogli a-derived cell-adhesive substrates that include a high molecular weigh t complex consisting of laminin beta-chains and proteoglycan (Matthies sen et al., 1989) stimulate neurite outgrowth, they fail to enhance lo ng-term neuronal survival when additional neurotrophic and cell-contac t interactions are lacking. Astrocytes release a diffusible neurotroph ic activity that, when permanently applied, maintains long-term surviv al of central neurons in culture. The soluble neurotrophic activity se ems to interact synergistically with cell-bound signals which are also required for long-term survival and which are expressed by astrocytes and neurons, but not by fibroblasts. Among neurons from different bra in areas, such as hippocampus, cerebral cortex and septum, regional di fferences in their responsiveness to the astroglial neurotrophic activ ity have been observed.