PLATELET-DERIVED GROWTH-FACTOR EXERTS TROPHIC EFFECTS ON RAT STRIATAL DARPP-32-CONTAINING NEURONS IN CULTURE
PLATELET-DERIVED GROWTH-FACTOR EXERTS TROPHIC EFFECTS ON RAT STRIATAL DARPP-32-CONTAINING NEURONS IN CULTURE
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DOI：
10.1007/bf00228749
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发表时间：
1994-09-01
影响因子：
2
通讯作者：
ODIN, P
中科院分区：
文献类型：
--
作者：
NAKAO, N;BRUNDIN, P;ODIN, P
本研究的目的是确定血小板衍生生长因子（PDGF）的两种亚型PDGF- aa和PDGF- bb是否在体外对发育中的大鼠纹状体神经元产生营养作用。采用免疫细胞化学方法鉴定纹状体神经元中多巴胺和腺苷3‘:5’单磷酸调节磷酸化蛋白（DARPP-32）的分子量为32千顿。在不含PDGF的对照培养中，体外培养第3至5天，darpp -32阳性神经元的平均数量减少了47%。PDGF-BB，而不是PDGF-AA，在第3天（42%）和第5天（149%）显著增加了darpp -32阳性神经元的数量。在对照和PDGF-BB处理的培养物中，细胞总数相似，这表明，在纹状体培养物中，PDGF-BB的作用对darpp -32阳性神经元是相对特异性的。与对照组和pdgf - aa处理的培养物相比，pdgf - bb处理的培养物中darpp -32阳性神经元的神经突更长，体细胞面积更大。我们的数据提供了证据，证明PDGF-BB通过促进细胞存活和形态分化对纹状体DARPP-32阳性神经元施加营养作用，尽管对神经元内DARPP-32水平也有刺激作用。这些发现提出了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的纹状体变性的可能性。
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 striatal 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.