Barnea A, Aguila-Mansilla N, Bigio E H, Worby C, Roberts J
Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center at Dallas, 75235-9032, USA.
Regul Pept. 1998 Sep 25;75-76:293-300. doi: 10.1016/s0167-0115(98)00081-0.
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.
我们实验室的一系列研究证实，原代培养的胎鼠和人神经肽Y（NPY）皮质神经元受到不同的调节。在一项初步研究中，我们发现原代星形胶质细胞会产生大量免疫反应性（IR）NPY。我们提出了一个问题：星形胶质细胞产生NPY-IR是一个受调控的过程吗？我们在大鼠和人原代星形胶质细胞培养物上测试了脑源性神经营养因子（BDNF，50 ng/ml）、碱性成纤维细胞生长因子（bFGF）、P物质（1 μM）、福斯可林（10 μM）或佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA，20 nM）对NPY-IR产生的影响。在这些试剂中，PMA和bFGF显著诱导大鼠和人星形胶质细胞产生NPY-IR，福斯可林诱导人星形胶质细胞而非大鼠星形胶质细胞产生NPY-IR，BDNF和P物质均未诱导大鼠或人星形胶质细胞产生NPY-IR。发现PMA诱导的NPY-IR的分子大小与前NPY一致。此外，PMA诱导了大小与神经元NPY-mRNA相对应的mRNA的积累。对人死后新皮层的免疫细胞化学分析显示，NPY-IR与星形胶质细胞标志物共存。这些结果表明，培养的星形胶质细胞以一种受调控的方式表达NPY基因，并且支持我们的观点，即在某些生理/病理条件下，原位反应性星形胶质细胞可能表达NPY基因。
