Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro

Trophic and protective actions of brain-derived neurotrophic factor on striatal DARPP-32-containing neurons in vitro
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DOI:
10.1016/0165-3806(96)83489-4
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发表时间:
1995-12-21
期刊:
DEVELOPMENTAL BRAIN RESEARCH
影响因子:
--
通讯作者:
Odin, P
Odin, P
中科院分区:
其他
文献类型:
--
作者:
Nakao, N;Brundin, P;Odin, P

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我们研究了脑源性神经营养因子 (BDNF)、血小板源性生长因子 BB 亚型 (PDGF-BB) 或这些生长因子的组合对无血清培养条件下生长的胚胎纹状体神经元的存活和形态发育的影响。使用免疫细胞化学对“多巴胺和腺苷 3”:5'-单磷酸调节的磷蛋白(分子量为 32 kilodalton)(DARPP-32)鉴定纹状体神经元。 BDNF和PDGF-BB促进了DARPP-32阳性神经元的存活,其作用的程度与它们带来的效果相当。这些生长因子的组合对细胞存活没有产生显着的附加效应。 BDNF 通过增加神经突的长度、神经突上的分支点的数量和体细胞面积来刺激含有 DARPP-32 的神经元的形态分化。相比之下,PDGF-BB增加了神经突长度和细胞体面积,但没有增加分支点的数量。 BDNF 还可以保护纹状体神经元免受 N-甲基-D-天冬氨酸诱导的兴奋性毒性,而 PDGF-BB 在与 BDNF 相同的治疗条件下没有效果。因此,BDNF在体外通过增强纹状体DARPP-32神经元的存活、形态分化和对兴奋性毒性的抵抗力来营养,其作用机制可能与PDGF-BB不同。
We have examined the effects of either brain-derived neurotrophic factor (BDNF), the BB-isoform of platelet-derived growth factor (PDGF-BB), or a combination of these growth factors on the survival and the morphological development of embryonic striatal neurons grown under serum-free culture conditions. Striatal neurons were identified using immunocytochemistry for ''dopamine- and adenosine 3':5'-monophosphate-regutated phosphoprotein with a molecular weight of 32 kilodalton'' (DARPP-32). BDNF and PDGF-BB promoted the survival of DARPP-32-positive neurons, with the magnitude of their effects bring comparable. A combination of these growth factors exerted no significant additive effects on cell survival. BDNF stimulated morphological differentiation of DARPP-32-containing neurons by increasing the length of neurites, the number of branching points on the neurites, and the soma area. By contrast, PDGF-BB increased the neurite length and the cell body area, but not the number of branching points. BDNF also protected striatal neurons from excitotoxicity induced by N-methyl-D-aspartate, whereas PDGF-BB had no effect under the same treatment conditions as those for BDNF. Thus, BDNF is trophic for striatal DARPP-32-containing neurons in vitro by enhancing the survival, morphological differentiation and resistance to excitotoxicity, and its mechanisms of action are probably different from those of PDGF-BB.