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暗饲养对神经营养因子Trk受体磷酸化的影响。

Effects of dark rearing on phosphorylation of neurotrophin Trk receptors.

作者信息

Viegi Alessandro, Cotrufo Tiziana, Berardi Nicoletta, Mascia Laura, Maffei Lamberto

机构信息

Scuola Normale Superiore, p.zza Dei Cavalieri, 7, 56126, Pisa, Italy.

出版信息

Eur J Neurosci. 2002 Nov;16(10):1925-30. doi: 10.1046/j.1460-9568.2002.02270.x.

Abstract

Total lack of visual experience (dark rearing, DR) is known to affect development of mammalian visual cortex (VC) and to prolong the critical period of visual cortical plasticity. Neurotrophins (NTs) have been proposed to play a relevant role in activity dependent processes important for the final shaping of cortical visual connections. Neurotrophin supply or antagonism of endogenous NT action profoundly affect visual cortical development and plasticity; in particular, exogenous supply of NTs counteracts DR effects on VC development. However, the effects of DR on NT expression are still debated and mounting evidence reports a mismatch between BDNF mRNA and protein expression in DR animals. To gain insight into the effects of DR on expression of nerve growth factor (NGF) and the functional state of NT signalling pathways, we assessed the phosphorylation state of Trk receptors in light-reared animals (LR), in dark-reared animals (DR), in DR animals briefly exposed to light and in DR animals with exogenous supply of NTs [NGF, brain-derived neurotrophic factor (BDNF) and NT-4] in the VC. We report that DR increases the expression of NGF but reduces the phosphorylation of TrkA and TrkB receptors with respect to LR; normal phosphorylation is rapidly rescued by a brief exposure to light. Exogenous supply of NGF, BDNF or NT4 in DR animals also rescues the phosphorylation of their receptors.

摘要

完全缺乏视觉体验(黑暗饲养,DR)已知会影响哺乳动物视觉皮层(VC)的发育,并延长视觉皮层可塑性的关键期。神经营养因子(NTs)被认为在对皮层视觉连接最终形成至关重要的活动依赖性过程中发挥相关作用。神经营养因子的供应或内源性NTs作用的拮抗作用会深刻影响视觉皮层的发育和可塑性;特别是,外源性供应NTs可抵消DR对VC发育的影响。然而,DR对NTs表达的影响仍存在争议,越来越多的证据表明DR动物中脑源性神经营养因子(BDNF)mRNA与蛋白表达之间存在不匹配。为了深入了解DR对神经生长因子(NGF)表达及NTs信号通路功能状态的影响,我们评估了在光照饲养动物(LR)、黑暗饲养动物(DR)、短暂暴露于光照的DR动物以及在VC中外源性供应NTs[NGF、脑源性神经营养因子(BDNF)和NT-4]的DR动物中Trk受体的磷酸化状态。我们报告称,与LR相比,DR增加了NGF的表达,但降低了TrkA和TrkB受体的磷酸化;短暂暴露于光照可迅速恢复正常磷酸化。在DR动物中外源性供应NGF、BDNF或NT4也可恢复其受体的磷酸化。

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