Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.

Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.
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DOI:
10.1073/pnas.91.20.9387
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发表时间:
1994-09
影响因子:
11.1
通讯作者:
R. Pinkas-Kramarski;R. Eilam;O. Spiegler;Sara Lavi;Naili Liu;David K. Chang;Duanzhi Wen;Michal Schwartz;Yosef Yarden
R. Pinkas-Kramarski;R. Eilam;O. Spiegler;Sara Lavi;Naili Liu;David K. Chang;Duanzhi Wen;Michal Schwartz;Yosef Yarden
中科院分区:
综合性期刊1区
文献类型:
--
作者:
R. Pinkas-Kramarski;R. Eilam;O. Spiegler;Sara Lavi;Naili Liu;David K. Chang;Duanzhi Wen;Michal Schwartz;Yosef Yarden

文献摘要

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Neu分化因子(NDF,也称为heregulin)基于其提高ErbB蛋白磷酸化的能力而从间充质细胞中分离。早期的原位杂交分析表明,NDF主要在胚胎发育过程中的中枢神经系统中转录。为了深入了解NDF在脑中的作用,我们通过免疫组织化学和原位杂交分析了其分布。妊娠晚期(第17天)大鼠胚胎在两个运动(例如,壳核)和边缘(例如,隔膜)区域。成人大脑中的NDF表达水平较低,但小脑除外,小脑中的NDF表达在出生后增加。神经元和神经胶质细胞都通过免疫组织化学鉴定为产生NDF的细胞(例如,大脑皮层中的锥体神经元和胼胝体中的神经胶质细胞)。通过建立大鼠脑细胞的原代培养,我们证实了NDF在神经元和星形胶质细胞中表达。此外,通过使用这样的原代培养物,我们观察到NDF处理仅产生有限的促有丝分裂作用,这伴随着星形胶质细胞成熟的显著加速。此外,长期孵育的因素,特别是保护星形胶质细胞的凋亡,这意味着NDF功能在大脑中作为一个生存和成熟的因素星形胶质细胞。
Neu differentiation factor (NDF, also called heregulin) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins. Earlier in situ hybridization analysis showed that NDF was transcribed predominantly in the central nervous system during embryonic development. To gain insights into the role of NDF in brain we analyzed its distribution by immunohistochemistry and in situ hybridization. Late-gestation (day 17) rat embryos displayed high NDF immunoreactivity in both motor (e.g., putamen) and limbic (e.g., septum) regions. Lower levels of the factor were exhibited by adult brain, except for the cerebellum, where NDF expression was increased postnatally. Both neurons and glial cells were identified by immunohistochemistry as NDF-producing cells (e.g., pyramidal neurons in the cerebral cortex and glial cells in the corpus callosum). By establishment of primary cultures of rat brain cells we confirmed that NDF was expressed in neurons as well as in astrocytes. In addition, by using such primary cultures we observed that NDF treatment exerted only a limited mitogenic effect, which was accompanied by significant acceleration of astrocyte maturation. Furthermore, long-term incubation with the factor specifically protected astrocytes from apoptosis, implying that NDF functions in brain as a survival and maturation factor for astrocytes.