Franklin Tamara B, Murphy Jeremy A, Myers Tanya L, Clarke David B, Currie R William
Laboratory of Molecular Neurobiology, Department of Anatomy and Neurobiology, Dalhousie University, Halifax, NS Canada B3H 1X5.
Brain Res. 2006 Jun 20;1095(1):1-11. doi: 10.1016/j.brainres.2006.04.025. Epub 2006 May 30.
The purpose of the present experiment was to characterize changes in TrkB signaling in the rat visual system resulting from exposure to enriched environment. Female Sprague-Dawley rats were placed in enriched or impoverished conditions for 1, 7 or 28 days. Levels of BDNF protein and its predominant receptor TrkB were examined in the retina, superior colliculus and visual cortex. In the retina, 1 day of enrichment increased full-length TrkB and after 28 days increased BDNF. In the superior colliculus, enrichment for 7 days reduced full-length TrkB and after 28 days increased BDNF and full-length TrkB. One day of enrichment significantly increased BDNF, reduced full-length TrkB and increased truncated TrkB in the visual cortex. Consequently, we further investigated whether exposure to enriched environment and the subsequent changes in BDNF and TrkB translates into a neuroprotective effect on retinal ganglion cells (RGCs) following transection of the optic nerve. Although exogenous intraocular application of BDNF provides neuroprotection to RGCs after axotomy, the endogenous increase in BDNF in the retina after 28 days of enrichment had no effect on RGC survival. While enriched housing conditions offer a model of non-invasive rehabilitation treatment for injury and modulates changes in BDNF and TrkB levels, these molecular changes did not translate into a neuroprotective effect on RGCs following transection of the optic nerve.
本实验的目的是描述暴露于丰富环境后大鼠视觉系统中TrkB信号的变化。将雌性Sprague-Dawley大鼠置于丰富或贫乏环境中1、7或28天。检测视网膜、上丘和视皮层中脑源性神经营养因子(BDNF)蛋白及其主要受体TrkB的水平。在视网膜中,1天的丰富环境会增加全长TrkB,28天后会增加BDNF。在上丘中,7天的丰富环境会降低全长TrkB,28天后会增加BDNF和全长TrkB。1天的丰富环境会显著增加视皮层中的BDNF,降低全长TrkB并增加截短型TrkB。因此,我们进一步研究了暴露于丰富环境以及随后BDNF和TrkB的变化是否对视神经横断后视网膜神经节细胞(RGC)产生神经保护作用。尽管眼内局部应用外源性BDNF在轴突切断后为RGC提供了神经保护,但丰富环境28天后视网膜中BDNF的内源性增加对RGC存活没有影响。虽然丰富的饲养条件为损伤提供了一种非侵入性康复治疗模型,并调节了BDNF和TrkB水平的变化,但这些分子变化对视神经横断后的RGC并没有产生神经保护作用。