EVIDENCE FOR REGULATED EXPRESSION OF NEUROPEPTIDE-Y GENE BY RAT AND HUMAN CULTURED ASTROCYTES

A series of studies from our laboratory have established that fetal ra t and human neuropeptide Y (NPY) cortical neurons in aggregate culture s are differentially regulated. In a preliminary study we found that p rimary astrocytes produce substantial amounts of immunoreactive (IR) N PY. We addressed the question: Is astrocyte production of NPY-IR a reg ulated process? The effects of brain-derived neurotrophic factor (BDNF , 50 ng/ml), basic fibroblast growth factor (bFGF), substance P(1 mu M ), forskolin (10 mu M), or phorbol 12-myristate-13-acetate (PMA, 20 nM ) on NPY-IR production was tested on rat and human primary astrocyte c ultures. Of these agents, PMA and bFGF markedly induced NPY-IR product ion by rat as well as human astrocytes, forskolin induced NPY-IR produ ction by human but not rat astrocytes, and neither BDNF nor substance P induced NPY-IR production by rat or human astrocytes. The molecular size of PMA-induced NPY-IR was found to be consistent with that of pro NPY. Moreover, PMA induced the accumulation of mRNA corresponding in s ize to the neuronal NPY-mRNA. Immunocytochemical analysis of human pos t-mortem neocortex revealed co-existence of NPY-IR with astrocyte mark ers. These results indicate that cultured astrocytes express NPY gene in a regulated manner and they support our proposition that in situ re active astrocytes may express NPY gene under some physiological/pathol ogical conditions. (C) 1998 Elsevier Science B.V. All rights reserved.