Zoology and ICORD (International Collaboration on Repair Discoveries), Blusson Spinal Cord Centre, 818 West 8th Avenue, Vancouver, BC, Canada V5Z 1M9.
Brain Res. 2010 Apr 6;1323:48-58. doi: 10.1016/j.brainres.2010.02.004. Epub 2010 Feb 6.
Spontaneous and/or treatment-evoked re-modeling of the CNS following spinal cord injury is a prerequisite for functional recovery. While there has been considerable interest in the role of endogenous neurotrophins in spontaneous plasticity of several populations of spinal axons, the same cannot be said for morphological changes to dendrites. Here, we examined the responses of dendrites in the mouse lateral spinal nucleus (LSN, a site of sensory integration in the dorsolateral white matter) to exogenous and endogenous neurotrophins. We performed a septuple dorsal rhizotomy, which permanently eliminates sensory input to the spinal cord, and stimulates sprouting of spinal axons. While dendrites showed no change in density following injury alone, they sprouted vigorously (a two-fold increase in density) upon addition of exogenous brain-derived neurotrophic factor (BDNF). On the other hand, endogenous nerve growth factor (NGF) severely restricted dendritic sprouting, as TrkA-Fc treatment also roughly doubled the density of dendritic processes in the LSN. Spontaneous, BDNF- and TrkA-Fc mediated sprouting was unaffected by the absence of p75(NTR). Importantly, TrkA-Fc treatment markedly reduced expression of the truncated BDNF receptor TrkBT1 in both p75(+/+) and p75(-/-) mice, which was robustly-upregulated by deafferentation in both genotypes. We propose that the upregulation of TrkBT1 by NGF results in a reduced availability of endogenous BDNF to dendrites. Accordingly, sprouting of serotonergic axons, a BDNF-dependent consequence of dorsal root injury, was significantly enhanced in TrkA-Fc-treated animals. These results suggest that NGF and BDNF signaling differentially regulates dendritic plasticity in the deafferented spinal cord.
脊髓损伤后中枢神经系统的自发和/或治疗诱发重塑是功能恢复的前提。虽然内源性神经营养因子在几种脊髓轴突群体的自发可塑性中发挥了相当大的作用，但树突形态的变化却不能这样说。在这里，我们研究了外源性和内源性神经营养因子对小鼠侧脊髓核（LSN，背外侧白质中感觉整合的部位）树突的反应。我们进行了七次背根切断术，这会永久性地消除脊髓的感觉输入，并刺激脊髓轴突的发芽。虽然单独损伤后树突的密度没有变化，但加入外源性脑源性神经营养因子（BDNF）后，它们大量发芽（密度增加了两倍）。另一方面，内源性神经生长因子（NGF）严重限制了树突的发芽，因为 TrkA-Fc 处理也使 LSN 中树突过程的密度大致增加了一倍。自发的、BDNF 和 TrkA-Fc 介导的发芽不受 p75(NTR)的缺失影响。重要的是，TrkA-Fc 处理显著降低了两种基因型中截断的 BDNF 受体 TrkBT1 的表达，而去传入神经在两种基因型中都强烈地上调了 TrkBT1 的表达。我们提出，NGF 上调 TrkBT1 会导致树突中内源性 BDNF 的可用性降低。因此，在 TrkA-Fc 处理的动物中，背根损伤依赖 BDNF 的 5-羟色胺能轴突发芽显著增强。这些结果表明，NGF 和 BDNF 信号通路以不同的方式调节去传入神经的脊髓中的树突可塑性。
