Gannon Sean M, Hawk Kiel, Walsh Brian F, Coulibaly Aminata, Isaacson Lori G
Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, United States; Department of Biology, Miami University, Oxford, OH 45056, United States.
Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, United States; Graduate Program in Cell, Molecular, and Structural Biology, Miami University, Oxford, OH 45056, United States.
Brain Res. 2018 Jul 15;1691:44-54. doi: 10.1016/j.brainres.2018.04.014. Epub 2018 Apr 19.
There is evidence that neuronal injury can affect uninjured neurons in the same neural circuit. The overall goal of this study was to understand the effects of peripheral nerve injury on uninjured neurons located in the central nervous system (CNS). As a model, we examined whether axotomy (transection of postganglionic axons) of the superior cervical ganglion (SCG) affected the uninjured, preganglionic neurons that innervate the SCG. At 7 days post-injury a reduction in choline acetyltransferase (ChAT) and synaptophysin immunoreactivity in the SCG, both markers for preganglionic axons, was observed, and this reduction persisted at 8 and 12 weeks post-injury. No changes were observed in the number or size of the parent cell bodies in the intermediolateral cell column (IML) of the spinal cord, yet synaptic input to the IML neurons was decreased at both 8 and 12 weeks post-injury. In order to understand the mechanisms underlying these changes, protein levels of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) were examined and reductions were observed at 7 days post-injury in both the SCG and spinal cord. Taken together these results suggest that axotomy of the SCG led to reduced BDNF in the SCG and spinal cord, which in turn influenced ChAT and synaptophysin expression in the SCG and also contributed to the altered synaptic input to the IML neurons. More generally these findings provide evidence that the effects of peripheral injury can cascade into the CNS and affect uninjured neurons.
有证据表明，神经元损伤可影响同一神经回路中未受损的神经元。本研究的总体目标是了解周围神经损伤对位于中枢神经系统（CNS）的未受损神经元的影响。作为一个模型，我们研究了颈上神经节（SCG）的轴突切断术（节后轴突横断）是否会影响支配SCG的未受损节前神经元。在损伤后7天，观察到SCG中胆碱乙酰转移酶（ChAT）和突触素免疫反应性降低，这两种都是节前轴突的标志物，并且这种降低在损伤后8周和12周持续存在。脊髓中间外侧细胞柱（IML）中母细胞体的数量和大小没有变化，但在损伤后8周和12周，IML神经元的突触输入均减少。为了了解这些变化的潜在机制，检测了脑源性神经营养因子（BDNF）和酪氨酸受体激酶B（TrkB）的蛋白水平，发现在损伤后7天，SCG和脊髓中的水平均降低。综合这些结果表明，SCG的轴突切断导致SCG和脊髓中BDNF减少，这反过来影响了SCG中ChAT和突触素的表达，也导致了IML神经元突触输入的改变。更普遍地说，这些发现提供了证据，表明周围损伤的影响可以级联到中枢神经系统并影响未受损的神经元。
