Othberg A, Odin P, Ballagi A, Ahgren A, Funa K, Lindvall O
Department of Neurology, University Hospital, Lund, Sweden.
Exp Brain Res. 1995;105(1):111-22. doi: 10.1007/BF00242187.
The neurotrophic effects of the BB isoform of platelet-derived growth factor (PDGF) on rat and human fetal mesencephalic dopaminergic neurons have been characterized in vitro. A dose-response analysis demonstrated maximal responses at 30 ng/ml of PDGF-BB. This concentration resulted in a marked increase in the survival and neurite outgrowth from rat and human tyrosine hydroxylase-(TH) positive, presumed dopaminergic neurons after 7 days in vitro. The effects of PDGF-BB on survival of TH-positive neurons were comparable to those of brain-derived neurotrophic factor (BDNF), whereas neurite outgrowth was more pronounced after addition of BDNF. The combination of BDNF and PDGF-BB yielded no additive effects. Double immunohistochemical staining of rat cultures demonstrated PDGF beta-receptors on about 90% of the TH-positive neurons. PDGF-BB treatment of rat mesencephalic cultures induced an upregulation of c-fos and TH mRNA with maximal levels after 0.5-2 h as assessed by quantitative PCR analysis. An increased number of Fos protein-positive cells was detected immunohistochemically after 4 h of PDGF-BB treatment. The present results provide further evidence for specific and direct effects of PDGF-BB on gene expression, survival and neurite outgrowth of mesencephalic dopaminergic neurons of rat and human origin.
血小板衍生生长因子（PDGF）的BB亚型对大鼠和人类胎儿中脑多巴胺能神经元的神经营养作用已在体外进行了表征。剂量反应分析表明，在30 ng/ml的PDGF-BB时出现最大反应。该浓度导致体外培养7天后，大鼠和人类酪氨酸羟化酶（TH）阳性的假定多巴胺能神经元的存活率和神经突生长显著增加。PDGF-BB对TH阳性神经元存活的影响与脑源性神经营养因子（BDNF）相当，而添加BDNF后神经突生长更明显。BDNF和PDGF-BB联合使用未产生叠加效应。对大鼠培养物进行双重免疫组化染色显示，约90%的TH阳性神经元上有PDGFβ受体。通过定量PCR分析评估，用PDGF-BB处理大鼠中脑培养物可诱导c-fos和TH mRNA上调，在0.5 - 2小时后达到最高水平。PDGF-BB处理4小时后，免疫组化检测到Fos蛋白阳性细胞数量增加。目前的结果为PDGF-BB对大鼠和人类中脑多巴胺能神经元的基因表达、存活和神经突生长的特异性和直接作用提供了进一步证据。
