Saini Vedangana, Loers Gabriele, Kaur Gurcharan, Schachner Melitta, Jakovcevski Igor
Zentrum für Molekulare Neurobiologie, Universitätskrankenhaus Hamburg-Eppendorf, Universität Hamburg, Hamburg, Germany.
Department of Biotechnology, Guru Nanak Dev University, Punjab, India.
Eur J Neurosci. 2016 Jul;44(1):1734-46. doi: 10.1111/ejn.13271. Epub 2016 May 31.
The neural cell adhesion molecule (NCAM) plays important functional roles in development of the nervous system. We investigated the influence of a constitutive ablation of NCAM on the outcome of spinal cord injury. Transgenic mice lacking NCAM (NCAM-/-) were subjected to severe compression injury of the lower thoracic spinal cord using wild-type (NCAM+/+) littermates as controls. According to the single-frame motion analysis, the NCAM-/- mice showed reduced locomotor recovery in comparison to control mice at 3 and 6 weeks after injury, indicating an overall positive impact of NCAM on recovery after injury. Also the Basso Mouse Scale score was lower in NCAM-/- mice at 3 weeks after injury, whereas at 6 weeks after injury the difference between genotypes was not statistically significant. Worse locomotor function was associated with decreased monoaminergic and cholinergic innervation of the spinal cord caudal to the injury site and decreased axonal regrowth/sprouting at the site of injury. Astrocytic scar formation at the injury site, as assessed by immunohistology for glial fibrillary acidic protein at and around the lesion site was increased in NCAM-/- compared with NCAM+/+ mice. Migration of cultured monolayer astrocytes from NCAM-/- mice was reduced as assayed by scratch wounding. Numbers of Iba-1 immunopositive microglia were not different between genotypes. We conclude that constitutive NCAM deletion in young adult mice reduces recovery after spinal cord injury, validating the hypothesized beneficial role of this molecule in recovery after injury.
神经细胞黏附分子（NCAM）在神经系统发育中发挥着重要的功能作用。我们研究了NCAM基因的组成性缺失对脊髓损伤结果的影响。以野生型（NCAM+/+）同窝小鼠作为对照，对缺乏NCAM的转基因小鼠（NCAM-/-）施加下胸段脊髓的严重压迫性损伤。根据单帧运动分析，与对照小鼠相比，NCAM-/-小鼠在损伤后3周和6周时运动功能恢复减少，表明NCAM对损伤后恢复具有总体积极影响。在损伤后3周时，NCAM-/-小鼠的Basso小鼠评分也较低，而在损伤后6周时，不同基因型之间的差异无统计学意义。较差的运动功能与损伤部位尾侧脊髓的单胺能和胆碱能神经支配减少以及损伤部位的轴突再生/芽生减少有关。通过对损伤部位及其周围的胶质纤维酸性蛋白进行免疫组织学评估，与NCAM+/+小鼠相比，NCAM-/-小鼠损伤部位的星形胶质细胞瘢痕形成增加。通过划痕损伤检测，NCAM-/-小鼠培养的单层星形胶质细胞的迁移减少。不同基因型之间Iba-1免疫阳性小胶质细胞的数量没有差异。我们得出结论，成年小鼠中NCAM基因的组成性缺失会降低脊髓损伤后的恢复，证实了该分子在损伤后恢复中的假定有益作用。
