OPPOSITE EFFECTS OF ASTROCYTE-DERIVED SOLUBLE FACTOR(S) ON THE FUNCTIONAL EXPRESSION OF FETAL PEPTIDERGIC NEURONS IN AGGREGATE CULTURES - ENHANCEMENT OF NEUROPEPTIDE-Y AND SUPPRESSION OF SOMATOSTATIN

Previous studies established that fetal rat and human neuropeptide Y ( NPY) cortical neurons in aggregate cultures are differentially regulat ed, Whereas brain-derived neurotrophic factor (BDNP) or phorbol 12-myr istate-13-acetate (PMA) induces NPY production in rat cultures, only P MA does so in human cultures, We addressed these questions: 1) Do solu ble products of rat or human astrocytes (conditioned medium; rCM and h CM, respectively) enhance the functional expression of cultured NPY ne urons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM spec ies specific? rCM enhanced (approximate to 2-fold) both basal and BDNF -stimulated production of NPY and coculture of rat aggregates and astr ocytes did not prevent this NPY-EA, Likewise, the hCM enhanced (approx imate to 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates, Moreover, the hCM enhanced NPY production by rat aggregat es and rCM enhanced NPY production by human aggregates, In addition, r CM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY prod uction by rat aggregates, Under each of the above conditions, the rCM/ hCM suppressed (approximate to 50%) production of SRIF by rat aggregat es, In summary, secretory products of rat and human astrocytes exert o pposite effects on the functional expression of NPY and SRIF neurons i n culture: enhancement of NPY and suppression of SRIF, By the criteria evaluated in this study, these astrocyte-derived activities do not ex hibit species specificity. (C) 1997 Wiley-Liss,Inc.