Developmental Brain Research, 31 (1987) 103-118 103 Elsevier BRD 50490 Rat astrocytes and Schwann cells in culture synthesize nerve growth factor-like neurite-promoting factors Jose G. Assouline 1, Peter Bosch 2, Ramon Lim 2, In Sook Kim 1, Robert Jensen I and Nicholas J. Pantazis 1 t Department of Anatomy, University of Iowa, Iowa City, 1A 52242 (U.S.A.) and 2Department of Neurology, University of lowa, Iowa City, IA 52242 (U.S.A.) (Accepted 29 July 1986) Key words: Neurite-promoting factor; Nerve growth factor; Astrocyte; Schwann cell Neurite-promoting activity in feeding medium conditioned by rat astrocytes and Schwann cells in culture was examined. The condi- tioned medium (CM) from both types of glial cultures stimulated extensive neurite outgrowth from embryonic chick dorsal root gan- glia (DRG) as well as pheochromocytoma (PC12) cells. Both the DRG and PC12 cells also produce neurite outgrowth in the presence of nerve growth factor (NGF). With the DRG, the neurite growth rates observed with the glial cell CM were identical to growth rates seen with NGF. Although anti-NGF antibody did not inhibit the neurite outgrowth produced by either of the glial CM, a nerve growth factor radioreceptor assay did detect an NGF-like molecule in both CM. Since the extensive neurite outgrowth stimulated by the glial CM was not mimicked by pure laminin alone, we conclude that the glial neurite promoting factors are distinct from laminin. INTRODUCTION Glial cells are believed to play important roles in neuronal cell development, maintenance and regen- eration 53. However, the mechanisms by which glial cells elicit these effects are not understood. The glial cells may synthesize various neuronotrophic and/or neurite promoting agents which interact directly with neuronal cells to either maintain these cells or stimu- late neuronal fiber outgrowth. Nerve growth factor (NGF) is a well-characterized neurite-promoting fac- tor which was originally discovered by Levi-Mon- talcini and Angeletti 24. NGF is synthesized by a va- riety of cells in culture including mouse fibroblast cells 38'4°'41, mouse S-180 cells is, muscle cells 35 and neuroblastoma 34. Whether or not glial cells synthesize NGF has not been clearly resolved. Burnham et al. 9 originally re- ported that non-neuronal cells derived from dorsal root ganglia (DRG) synthesize factors which could substitute for NGF and provide trophic support for neuronal cells. However, the identity of the trophic factor as NGF was disputed 31 by other investigators who could not block the effects of the trophic factor by anti-NGF antibody. In other studies, rat glial tumors 2s and a rat glial cell line, C636, were re- ported to synthesize NGF but again other research- ers ~4 disagreed with the conclusion that the neurite promoting factor was NGF. Studies with non-trans- formed astrocyte cultures also yielded conflicting re- sults. Lindsay 27 found that rat brain astrocytes syn- thesized both an NGF-like molecule which was blocked by anti-NGF antibody as well as a non-NGF agent which supported the survival of NGF-insensi- tive neurons, such as sensory neurons from the no- dose ganglion. Norrgren et al. 37 reported that human brain astrocytes in culture synthesized an NGF-like molecule which was inhibited by anti-NGF antibody. In contrast, Miiller et al. 33 found that primary rat as- trocytes in culture synthesized a low-molecular- Correspondence: N.J. Pantazis, Department of Anatomy, BSB 1-430, University of Iowa Medical College, Iowa City, IA 52242, U.S.A. 0165-3806/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)