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成熟和老龄交感神经元对层粘连蛋白和神经生长因子的反应:一项体外研究

Responses of mature and aged sympathetic neurons to laminin and NGF: an in vitro study.

作者信息

Cowen T, Jenner C, Song G X, Santoso A W, Gavazzi I

机构信息

Department of Anatomy and Developmental Biology, Royal Free Hospital School of Medicine, London, United Kingdom.

出版信息

Neurochem Res. 1997 Aug;22(8):1003-11. doi: 10.1023/a:1022478926949.

Abstract

Whilst the potent effects of NGF and laminin on developing neurons are well documented, relatively little is known about the effects of, or altered availability of or altered responsiveness to, these substances on the growth of adult neurons. We have therefore examined this question using explant cultures of sympathetic neurons from the superior cervical ganglion (SCG) of mature and aged rats. Explants were grown on substrata containing different doses of laminin, either with or without added NGF in culture medium containing FCS. Individually, laminin and NGF had relatively small effects on neurite outgrowth and length, which tended to be reduced in old neurons. In contrast, laminin in the presence of exogenous NGF exerted a powerful effect on nerve growth which was substantially greater than the sum of the effects of the individual factors. This synergy was evident in all experimental groups and was greatest in old explants at high doses of laminin, where growth was comparable to that of mature neurons. The dose-response curve of old neurons to laminin in the presence of added NGF indicated reduced responsiveness. These results suggest that variations in the availability of laminin and/or exogenous NGF, together with altered patterns of neuronal responsiveness, may contribute to impaired neuronal plasticity in old age.

摘要

虽然神经生长因子(NGF)和层粘连蛋白对发育中神经元的强大作用已有充分记载,但对于这些物质对成年神经元生长的影响、其可利用性的改变或反应性的改变,人们了解得相对较少。因此,我们使用来自成熟和老龄大鼠颈上神经节(SCG)的交感神经元外植体培养物来研究这个问题。外植体在含有不同剂量层粘连蛋白的基质上生长,培养基中添加或不添加NGF,同时含有胎牛血清(FCS)。单独来看,层粘连蛋白和NGF对神经突生长和长度的影响相对较小,老龄神经元中的这些影响往往会减弱。相比之下,在外源性NGF存在的情况下,层粘连蛋白对神经生长具有强大的作用,其作用远大于单个因子作用的总和。这种协同作用在所有实验组中都很明显,在高剂量层粘连蛋白的老龄外植体中最为显著,此时的生长与成熟神经元相当。在添加NGF的情况下,老龄神经元对层粘连蛋白的剂量反应曲线表明其反应性降低。这些结果表明,层粘连蛋白和/或外源性NGF可利用性的变化,以及神经元反应模式的改变,可能导致老龄时神经元可塑性受损。

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