NEUROTROPHIC EFFECTS OF THE PINEAL-GLAND - ROLE OF NONNEURONAL CELLS IN COCULTURES OF THE PINEAL-GLAND AND SUPERIOR CERVICAL-GANGLIA

The pineal gland (PG) is a source of several trophic factors, In this study, PG and superior cervical ganglia (SCG) from Sprague-Dawley neon ates (1-day-old) were co-cultured to test the hypothesis that endogeno us release of PG NGF (or an NGF-like cytokine) is sufficient to promot e survival of SCG neurons. Neuronal density of SCG neurons was signifi cantly enhanced when co-cultured with PG for 7 days compared to SCG cu ltured alone, SCG survival and neurite formation in PG co-cultures was less than in SCG treated with exogenous NGF (100 ng/ml). The neurotro phic effect of PG co-cultures was abolished when 1% anti-NGF was added to the medium. Go-cultures of SCG neurons with established 7-day PG c ultures induced extensive SCG neurite formation within 24 hr compared to SCG co-cultured with 1-day PG cultures. This suggests that PG neuro trophic effects are due to PG non-neuronal cells (nnc) that proliferat e to confluency by 7 days in culture, S-antigen-positive pinealocytes did not proliferate in culture. There was decreased SCG survival when neurons were seeded onto PG cultures that had been previously killed b y drying, which suggests that the neurotrophic effects of nnc are not substrate-dependent. Immunocytochemical characterization of PG nnc rev ealed a heterogenous mixture of astrocytes, macrophage/microglia, and fibroblasts, These findings support the hypothesis that NGF is activel y secreted by PG and that nnc are the principal source of this neuroto phin.