Farkas L M, Suter-Crazzolara C, Unsicker K
Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
J Neurosci Res. 1997 Nov 1;50(3):361-72. doi: 10.1002/(SICI)1097-4547(19971101)50:3<361::AID-JNR2>3.0.CO;2-G.
Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent neurotrophic factor for several neuron populations in the central and peripheral nervous system. Members of the neurotrophin, neurokine, and TGF-beta families of growth factors can affect neurons beyond their capacity to promote survival. They can play instructive roles including the determination of a particular transmitter phenotype. Here, we show that GDNF enhances the number of calretinin (CaR)-positive neurons in serum-free cultures of striatal cells isolated from embryonic rats. The effect is dose-dependent, can be elicited with concentrations as low as 0.1 ng/ml, and is not accompanied by increased incorporation of 5-bromo-2'-desoxyuridine and appearance of glial fibrillary acidic protein-positive cells. Similar, but weaker effects can be elicited by brain-derived neurotrophic factor, neurotrophin-3 and -4, fibroblast growth factor-2. Ciliary neurotrophic factor, nerve growth factor, and TGF-beta 1 do not affect striatal CaR expression. GDNF can augment CaR-positive cells at any time point and with a minimal exposure of 18 hr, suggesting induction of the phenotype rather than increased survival. By reverse transcription polymerase chain reaction (RT-PCR), we show that GDNF is expressed in the E16 striatum and in cultures derived from this tissue. GDNF also protected striatal CaR-positive neurons against glutamate toxicity. We conclude that striatal GDNF, in addition to its retrograde trophic role for nigrostriatal dopaminergic neurons, may also act locally within the striatum (e.g., by inducing the CaR phenotype and protecting these cells against toxic insult).
胶质细胞源性神经营养因子（GDNF）是转化生长因子-β（TGF-β）超家族的成员，是中枢和外周神经系统中几种神经元群体的强效神经营养因子。神经营养因子、神经激肽和TGF-β家族的生长因子成员对神经元的影响可能超出其促进存活的能力。它们可以发挥指导作用，包括决定特定的递质表型。在这里，我们表明GDNF可增加从胚胎大鼠分离的纹状体细胞无血清培养物中钙视网膜蛋白（CaR）阳性神经元的数量。这种作用是剂量依赖性的，低至0.1 ng/ml的浓度即可引发，且不伴有5-溴-2'-脱氧尿苷掺入增加和胶质纤维酸性蛋白阳性细胞的出现。脑源性神经营养因子、神经营养因子-3和-4、成纤维细胞生长因子-2可引发类似但较弱的作用。睫状神经营养因子、神经生长因子和TGF-β1不影响纹状体CaR表达。GDNF可在任何时间点增加CaR阳性细胞，最短暴露18小时即可，这表明是表型诱导而非存活增加。通过逆转录聚合酶链反应（RT-PCR），我们表明GDNF在E16纹状体及其衍生的培养物中表达。GDNF还可保护纹状体CaR阳性神经元免受谷氨酸毒性。我们得出结论，纹状体GDNF除了对黑质纹状体多巴胺能神经元具有逆行营养作用外，还可能在纹状体内局部发挥作用（例如，通过诱导CaR表型并保护这些细胞免受毒性损伤）。
