Béchade Catherine, Mallecourt Catherine, Sedel Frédéric, Vyas Sheela, Triller Antoine
Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, Institut National de la Santé et de la Recherche Médicale U497, Ecole Normale Supérieure, 75005 Paris, France.
J Neurosci. 2002 Oct 15;22(20):8779-84. doi: 10.1523/JNEUROSCI.22-20-08779.2002.
Rat spinal cord interneurons undergo programmed cell death shortly after birth. We investigated here whether cell death of interneurons could be regulated by trophic factors produced by motoneurons, one of their main targets. To test this hypothesis, we studied the effect of the selective destruction of motoneurons on the survival of interneurons in organotypic cultures of embryonic rat spinal cords. Motoneurons were eliminated by an anti-p75(NTR)-specific immunotoxin (192 IgG-saporin). We then observed a decrease of 28% in the number of ventral spinal interneurons immunoreactive (IR) for the homeoprotein PAX2. This was correlated with an increase in the number of apoptotic nuclei in the same area. Because neurotrophin-3 (NT-3) is specifically produced by motoneurons and because interneurons express the NT-3 high-affinity receptor trkC, we examined the role of NT-3 in the survival of PAX2-IR interneurons. Addition of NT-3 to 192 IgG-saporin-treated explants rescued ventral PAX2-IR interneurons. Depletion of secreted NT-3 by anti-NT-3 antibodies induced 66% loss of ventral PAX2-IR interneurons. We conclude that motoneuron-derived NT-3 is a trophic factor for ventral PAX2-IR interneurons.
大鼠脊髓中间神经元在出生后不久便会经历程序性细胞死亡。我们在此研究了中间神经元的细胞死亡是否可由其主要靶标之一的运动神经元产生的营养因子所调节。为验证这一假设，我们在胚胎大鼠脊髓的器官型培养物中研究了运动神经元选择性破坏对中间神经元存活的影响。通过抗p75（NTR）特异性免疫毒素（192 IgG-皂草素）消除运动神经元。然后我们观察到，对同源结构域蛋白PAX2呈免疫反应性（IR）的脊髓腹侧中间神经元数量减少了28%。这与同一区域凋亡细胞核数量的增加相关。由于神经营养因子-3（NT-3）由运动神经元特异性产生，且中间神经元表达NT-3高亲和力受体trkC，我们研究了NT-3在PAX2-IR中间神经元存活中的作用。向经192 IgG-皂草素处理的外植体中添加NT-3可挽救脊髓腹侧PAX2-IR中间神经元。用抗NT-3抗体耗尽分泌的NT-3会导致脊髓腹侧PAX2-IR中间神经元损失66%。我们得出结论，运动神经元衍生的NT-3是脊髓腹侧PAX2-IR中间神经元的一种营养因子。
