Kuo L-T, Groves M J, Scaravilli F, Sugden D, An S F
Department of Molecular Neuroscience, Division of Neuropathology, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Neuroscience. 2007 Jun 29;147(2):491-507. doi: 10.1016/j.neuroscience.2007.04.023. Epub 2007 May 29.
In the months following transection of adult rat peripheral nerve some sensory neurons undergo apoptosis. Two weeks after sciatic nerve transection some neurons in the L4 and L5 dorsal root ganglia begin to show immunoreactivity for nestin, a filament protein expressed by neuronal precursors and immature neurons, which is stimulated by neurotrophin-3 (NT-3) administration. The aim of this study was to examine whether NT-3 administration could be compensating for decreased production of neurotrophins or their receptors after axotomy, and to determine the effect on nestin synthesis. The levels of mRNA in the ipsilateral and contralateral L4 and L5 dorsal root ganglia were analyzed using real-time polymerase chain reaction, 1 day, 1, 2 and 4 weeks after unilateral sciatic nerve transection and NT-3 or vehicle administration via s.c. micro-osmotic pumps. In situ hybridization was used to identify which cells and neurons expressed mRNAs of interest, and the expression of full-length trkC and p75NTR protein was investigated using immunohistochemistry. Systemic NT-3 treatment increased the expression of brain-derived neurotrophic factor, nestin, trkA, trkB and trkC mRNA in ipsilateral ganglia compared with vehicle-treated animals. Some satellite cells surrounding neurons expressed trkA and trkC mRNA and trkC immunoreactivity. NT-3 administration did not affect neurotrophin mRNA levels in the contralateral ganglia, but decreased the expression of trkA mRNA and increased the expression of trkB mRNA and p75NTR mRNA and protein. These data suggest that systemically administered NT-3 may counteract the decrease, or even increase, neurotrophin responsiveness in both ipsi- and contralateral ganglia after nerve injury.
在成年大鼠外周神经横断后的数月里，一些感觉神经元会发生凋亡。坐骨神经横断两周后，L4和L5背根神经节中的一些神经元开始对巢蛋白呈现免疫反应性，巢蛋白是一种由神经元前体和未成熟神经元表达的丝状蛋白，其表达可被神经营养因子-3（NT-3）给药所刺激。本研究的目的是检测给予NT-3是否能够补偿轴突切断后神经营养因子或其受体产生的减少，并确定其对巢蛋白合成的影响。在单侧坐骨神经横断并通过皮下微渗透泵给予NT-3或赋形剂后1天、1周、2周和4周，使用实时聚合酶链反应分析同侧和对侧L4和L5背根神经节中的mRNA水平。原位杂交用于鉴定哪些细胞和神经元表达感兴趣的mRNA，并使用免疫组织化学研究全长trkC和p75NTR蛋白的表达。与给予赋形剂的动物相比，全身性NT-3治疗增加了同侧神经节中脑源性神经营养因子、巢蛋白、trkA、trkB和trkC mRNA的表达。神经元周围的一些卫星细胞表达trkA和trkC mRNA以及trkC免疫反应性。给予NT-3不影响对侧神经节中的神经营养因子mRNA水平，但降低了trkA mRNA表达并增加了trkB mRNA和p75NTR mRNA及蛋白的表达。这些数据表明，全身性给予NT-在神经损伤后可能会抵消同侧和对侧神经节中神经营养因子反应性的降低，甚至增加其反应性。
