PDGF‐BB Exerts Trophic Activity on Cultured GABA Interneurons from the Newborn Rat Cerebellum

PDGF‐BB Exerts Trophic Activity on Cultured GABA Interneurons from the Newborn Rat Cerebellum
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PDGF-BB 对新生大鼠小脑培养的 GABA 中间神经元发挥营养活性

DOI:
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发表时间:
1993
影响因子:
3.4
通讯作者:
K. Funa
K. Funa
中科院分区:
医学3区
文献类型:
--
作者:
A. Smits;A. Ballagi;K. Funa

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血小板源性生长因子(PDGF)是间充质源性细胞和神经胶质细胞的一种众所周知的有丝分裂原。其存在于中枢神经系统的神经元细胞中只是最近才被描述。我们先前已经表明,培养的新生大鼠脑神经元表达PDGF β受体,并且PDGF B-链的同源二聚体PDGF-BB增加新生小脑细胞的存活并促进神经突生长(Smits等人,美国国家科学院院报Sci. USA,88,8159 - 8163,1991)。本研究进一步探讨PDGF对生后早期大鼠小脑细胞的影响。通过使用化学成分确定的无血清培养基,我们建立了大鼠小脑(出生后4 - 5天)的原代细胞培养物,其中含有70 - 80%的神经元细胞。在体外的前10天内,在PDGF-BB-处理的和未处理的培养物之间没有发现总细胞数的差异。在体外培养的前10天内,向培养物中加入PDGF-BB导致表达谷氨酸脱羧酶(GAD)(GABA生物合成酶)的中间神经元的存活率相对增加。此外,在未处理的细胞培养物中添加PDGF-BB导致GAD mRNA的快速增加。这些结果表明,PDGF-BB作为小脑GABA能中间神经元的营养因子,通过上调GAD合成并延长这些细胞的存活。此外,原位杂交显示,在出生后早期小脑中存在表达PDGF β受体mRNA的散在细胞。这些细胞在分子层和内部颗粒层附近的定位与发育中小脑中GABA能中间神经元的定位相对应。
Platelet‐derived growth factor (PDGF) is a well known mitogen for mesenchyme‐derived cells and glial cells. Its presence in neuronal cells of the central nervous system has only recently been described. We have shown earlier that neurons of newborn rat brains in culture express PDGF β‐receptors and that PDGF‐BB, a homodimer of PDGF B‐chain, increases survival and promotes neurite outgrowth of newborn cerebellar cells (Smits et al., Proc. Natl Acad. Sci. USA, 88, 8159 – 8163, 1991). In this study, the effects of PDGF on early postnatal rat cerebellar cells were further explored. By using chemically defined serum‐free medium, we have established primary cell cultures of rat cerebella (postnatal day 4 – 5) containing 70 – 80% neuronal cells. During the first 10 days in vitro, no difference in total cell number was found between PDGF‐BB‐treated and untreated cultures. After this time period, however, increased survival of the PDGF‐BB‐treated cells was found. Within the first 10 days in vitro, the addition of PDGF‐BB to the cultures resulted in a relative increase in survival of interneurons expressing glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. Moreover, addition of PDGF‐BB in the untreated cell culture resulted in a rapid increase of GAD mRNA. These results show that PDGF‐BB acts as a trophic factor on GABAergic interneurons of the cerebellum by up‐regulating GAD synthesis and prolonging the survival of these cells. Furthermore, in situ hybridization revealed that there are scattered cells present in the early postnatal cerebellum that express PDGF β‐receptor mRNA. The localization of these cells in the molecular layer and in the proximity of the internal granular layer corresponds to that of GABAergic interneurons in the developing cerebellum.
发育中大鼠小脑中谷氨酸脱羧酶信使 RNA 的定量原位杂交分析。
DOI: 10.1016/0165-3806(91)90085-w
发表时间: 1991
期刊: Brain research. Developmental brain research
影响因子: --
作者:
Willcutts,MD;Morrison-Bogorad,M
通讯作者: Morrison-Bogorad,M