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 rat and human neuropeptide Y (NPY) cortical neurons in aggregate cultures are differentially regulated. In a preliminary study we found that primary astrocytes produce substantial amounts of immunoreactive (IR) NPY. We addressed the question: Is astrocyte production of NPY-IR a regulated process? The effects of brain-derived neurotrophic factor (BDNF, 50 ng/ml), basic fibroblast growth factor (bFGF), substance P (1 microM), forskolin (10 microM), or phorbol 12-myristate-13-acetate (PMA, 20 nM) on NPY-IR production was tested on rat and human primary astrocyte cultures. Of these agents, PMA and bFGF markedly induced NPY-IR production by rat as well as human astrocytes, forskolin induced NPY-IR production 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 proNPY. Moreover, PMA induced the accumulation of mRNA corresponding in size to the neuronal NPY-mRNA. Immunocytochemical analysis of human post-mortem neocortex revealed co-existence of NPY-IR with astrocyte markers. These results indicate that cultured astrocytes express NPY gene in a regulated manner and they support our proposition that in situ reactive astrocytes may express NPY gene under some physiological/pathological conditions.
Barnea
A
A
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center at Dallas, 75235-9032, USA. abarn1@mednet.swmed.edu
Aguila-Mansilla
N
N
Bigio
E H
EH
Worby
C
C
Roberts
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019579:Neocortex / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D018040:Receptors, Neurokinin-1; D016222:Fibroblast Growth Factor 2; D005576:Colforsin; D013373:Substance P; D020794:Receptor Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate