Gonzalez-Perez Francisco, Alé Albert, Santos Daniel, Barwig Christina, Freier Thomas, Navarro Xavier, Udina Esther
Institute of Neurosciences, Department of Cell Biology, Physiology, Immunology, Universitat Autònoma de Barcelona, CIBERNED, E-08193, Bellaterra, Spain.
Medovent GmbH, Mainz, Germany.
Eur J Neurosci. 2016 Feb;43(3):431-42. doi: 10.1111/ejn.13057. Epub 2015 Sep 30.
After peripheral nerve injuries, damaged axons can regenerate but functional recovery is limited by the specific reinnervation of targets. In this study we evaluated if motor and sensory neurites have a substrate preference for laminin and fibronectin in postnatal and adult stages. In postnatal dorsal root ganglia (DRG) explants, sensory neurons extended longer neurites on collagen matrices enriched with laminin (50%) or fibronectin (35%), whereas motoneurons extended longer neurites (~100%) in organotypic spinal cord slices embedded in fibronectin-enriched matrix. An increased percentage of parvalbumin-positive neurites (presumptive proprioceptive) vs. neurofilament-positive neurites was also found in DRG in fibronectin-enriched matrix. To test if the different preference of neurons for extracellular matrix components was maintained in vivo, these matrices were used to fill a chitosan guide to repair a 6-mm gap in the sciatic nerve of adult rats. However, the number of regenerating motor and sensory neurons after 1 month was similar between groups. Moreover, none of the retrotraced sensory neurons in DRG was positive for parvalbumin, suggesting that presumptive proprioceptive neurons had poor regenerative capabilities compared with other peripheral neurons. Using real-time PCR we evaluated the expression of α5β1 (receptor for fibronectin) and α7β1 integrin (receptor for laminin) in spinal cord and DRG 2 days after injury. Postnatal animals showed a higher increase of α5β1 integrin, whereas both integrins were similarly expressed in adult neurons. Therefore, we conclude that motor and sensory axons have a different substrate preference at early postnatal stages but this difference is lost in the adult.
周围神经损伤后,受损轴突能够再生,但功能恢复受到靶标特异性再支配的限制。在本研究中,我们评估了运动和感觉神经突在出生后和成年阶段对层粘连蛋白和纤连蛋白是否具有底物偏好。在出生后背根神经节(DRG)外植体中,感觉神经元在富含层粘连蛋白(约50%)或纤连蛋白(约35%)的胶原基质上延伸出更长的神经突,而运动神经元在嵌入富含纤连蛋白基质的脊髓器官型切片中延伸出更长的神经突(约100%)。在富含纤连蛋白的基质中的DRG中,还发现小白蛋白阳性神经突(推测为本体感觉神经突)与神经丝阳性神经突的比例增加。为了测试神经元对细胞外基质成分的不同偏好是否在体内得以维持,这些基质被用于填充壳聚糖导管,以修复成年大鼠坐骨神经6毫米的间隙。然而,1个月后再生的运动和感觉神经元数量在各组之间相似。此外,DRG中逆行追踪的感觉神经元均无小白蛋白阳性,这表明与其他周围神经元相比,推测的本体感觉神经元的再生能力较差。我们使用实时PCR评估了损伤后2天脊髓和DRG中α5β1(纤连蛋白受体)和α7β1整合素(层粘连蛋白受体)的表达。出生后的动物显示出α5β1整合素的更高增加,而两种整合素在成年神经元中表达相似。因此,我们得出结论,运动和感觉轴突在出生后早期具有不同的底物偏好,但这种差异在成年后消失。