Nakao N, Brundin P, Funa K, Lindvall O, Odin P
Department of Neurology, University Hospital, Lund, Sweden.
Exp Brain Res. 1994;101(2):291-6. doi: 10.1007/BF00228749.
The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat strial neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF-BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.
本研究的目的是确定血小板衍生生长因子(PDGF)的两种同工型,即PDGF-AA和PDGF-BB,是否在体外对发育中的大鼠纹状体神经元发挥营养作用。使用针对分子量为32千道尔顿的多巴胺和3':5'-单磷酸腺苷调节磷蛋白(DARPP-32)的免疫细胞化学方法鉴定纹状体神经元。在没有PDGF的对照培养物中,体外培养第3至5天时,DARPP-32阳性神经元的平均数量减少了47%。PDGF-BB而非PDGF-AA,在第3天(增加42%)和第5天(增加149%)均显著增加了DARPP-32阳性神经元的数量。对照培养物和经PDGF-BB处理的培养物中的总细胞数相似,这表明在纹状体培养物中,PDGF-BB的作用对DARPP-32阳性神经元具有相对特异性。与对照培养物和经PDGF-AA处理的培养物相比,经PDGF-BB处理的培养物中的DARPP-32阳性神经元具有更长的神经突和更大的胞体面积。我们的数据提供了证据,表明PDGF-BB通过促进细胞存活和形态分化,在体外对纹状体DARPP-32阳性神经元发挥营养作用,尽管对神经元内DARPP-32水平也可能有刺激作用。这些发现增加了一种可能性,即PDGF-BB也可能参与体内纹状体神经元的发育和维持,并可用于对抗亨廷顿病模型中的纹状体退化。