Lindå H, Shupliakov O, Ornung G, Ottersen O P, Storm-Mathisen J, Risling M, Cullheim S
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Comp Neurol. 2000 Sep 11;425(1):10-23.
After axotomy in the ventral funiculus of the cat spinal cord, about half of the population of lesioned motoneurons die at 1-3 weeks postoperatively, whereas the other half survives and generates new axons through the lesion area. To identify conditions that may promote survival and regeneration of motoneurons subjected to this kind of injury, the authors examined ultrastructurally lesion-induced changes in the number and distribution of nerve terminals on the somata and proximal dendrites of alpha-motoneurons in the 7th lumbar spinal segment (L7) of the cat spinal cord. Intramedullary axotomy resulted in a profound reduction in the number of nerve terminals impinging on the somata and proximal dendrites, with the maximal effect seen at 3 weeks postlesion. At that time, only 12-25% of the normal number of terminals remained on the cell somata, and 22-33% remained on proximal dendrites. Thereafter, a gradual increase in terminal numbers occurred, reaching normal levels at 34 weeks after the lesion. Already at 2 days postoperatively and, most obviously, at 3 weeks postoperatively, type S nerve terminals were eliminated to a larger degree than type F terminals. Postembedding immunohistochemistry confirmed that the largest reduction at 3 weeks was seen for excitatory glutamate-immunopositive type S nerve terminals (90%), whereas inhibitory glycine-immunoreactive and gamma-aminobutyric acid (GABA)-immunoreactive type F terminals were affected less (70% reduction). This led to a distinct shift in the ratio between the numbers of terminals that were immunopositive for glycine and GABA and the numbers of terminals that were labeled for glutamate. For the cell body, this ratio increased from 3.7 in normal material to 14.5 in lesioned motoneurons, whereas the corresponding values for proximal dendrites were 3.8 and 7.5. The preferential elimination of glutamatergic inputs to lesioned motoneurons may reflect an active reorganization of the synaptic input to diminish the excitotoxic influence on these neurons, thereby promoting the survival of motoneurons after intramedullary axotomy.
猫脊髓腹侧索切断轴突后，约一半受损运动神经元在术后1 - 3周死亡，而另一半存活并通过损伤区域长出新轴突。为了确定可能促进遭受此类损伤的运动神经元存活和再生的条件，作者对猫脊髓第7腰段（L7）α运动神经元胞体和近端树突上神经末梢数量和分布的损伤诱导变化进行了超微结构检查。髓内轴突切断导致投射到胞体和近端树突上的神经末梢数量大幅减少，损伤后3周时效果最为明显。此时，细胞胞体上仅留存正常数量末梢的12 - 25%，近端树突上留存22 - 33%。此后，末梢数量逐渐增加，在损伤后34周达到正常水平。术后2天就已出现，最明显的是在术后3周，S型神经末梢比F型末梢被消除的程度更大。包埋后免疫组织化学证实，3周时兴奋性谷氨酸免疫阳性的S型神经末梢减少最多（90%），而抑制性甘氨酸免疫反应性和γ-氨基丁酸（GABA）免疫反应性的F型末梢受影响较小（减少70%）。这导致甘氨酸和GABA免疫阳性的末梢数量与谷氨酸标记的末梢数量之比发生明显变化。对于细胞体，该比例从正常材料中的3.7增加到受损运动神经元中的14.5，而近端树突的相应值分别为3.8和7.5。对受损运动神经元谷氨酸能输入的优先消除可能反映了突触输入的主动重组，以减少对这些神经元的兴奋性毒性影响，从而促进髓内轴突切断后运动神经元的存活。
