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.

Abstract

Previous studies established that fetal rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. Whereas brain-derived neurotrophic factor (BDNF) or phorbol 12-myristate-13-acetate (PMA) induces NPY production in rat cultures, only PMA does so in human cultures. We addressed these questions: 1) Do soluble products of rat or human astrocytes (conditioned medium; rCM and hCM, respectively) enhance the functional expression of cultured NPY neurons and if so, do they enhance the expression of somatostatin (SRIF) neurons as well? 2) Is the NPY-enhancing activity (EA) in the CM species specific? rCM enhanced (approximately 2-fold) both basal and BDNF-stimulated production of NPY and coculture of rat aggregates and astrocytes did not prevent this NPY-EA. Likewise, the hCM enhanced (approximately 2.5-fold) basal and PMA-stimulated production of NPY by human aggregates. Moreover, the hCM enhanced NPY production by rat aggregates and rCM enhanced NPY production by human aggregates. In addition, rCM and hCM each enhanced BDNF-, forskolin-, or PMA-stimulated NPY production by rat aggregates. Under each of the above conditions, the rCM/hCM suppressed (approximately 50%) production of SRIF by rat aggregates. In summary, secretory products of rat and human astrocytes exert opposite effects on the functional expression of NPY and SRIF neurons in culture: enhancement of NPY and suppression of SRIF. By the criteria evaluated in this study, these astrocyte-derived activities do not exhibit species specificity.