Histone H1 improves regeneration after mouse spinal cord injury and changes shape and gene expression of cultured astrocytes
Histone H1 improves regeneration after mouse spinal cord injury and changes shape and gene expression of cultured astrocytes
复制标题
DOI：
10.3233/rnn-190903
复制
发表时间：
2019-01-01
影响因子：
2.8
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
--
作者：
Kleene, Ralf;Loers, Gabriele;Schachner, Melitta
背景资料：我们已经表明，组蛋白H1是一个结合伴侣的聚唾液酸（PSA），它提高了功能恢复，轴突再生/发芽，和目标renervation后小鼠股nerve injury.Objective：在这里，我们分析了组蛋白H1是否影响功能恢复，轴突再生/发芽，和目标renervation后脊髓损伤的成年小鼠。此外，我们测试了在体外组蛋白H1的星形胶质细胞基因表达，细胞的形状和迁移，以及对细胞的生存培养motoneurs.Methods：我们应用组蛋白H1压缩脊髓和确定功能恢复和数量的胶质酸性蛋白（GFAP）和神经元胶质抗原2（NG 2）阳性胶质细胞，这有助于胶质瘢痕。组蛋白H1的星形胶质细胞，星形胶质细胞基因表达和运动神经元的存活率迁移的影响，确定使用划痕受伤的星形胶质细胞单层培养，星形胶质细胞培养物的微阵列分析，和运动神经元细胞培养氧化应激conditions.Results：组蛋白H1的应用提高运动功能，增强单胺能和胆碱能神经支配的脊髓。损伤后6周，组蛋白H1处理的小鼠损伤部位周围GFAP和NG 2的表达水平相对于溶剂处理的小鼠降低。组蛋白H1减少星形胶质细胞迁移，改变GFAP和NG 2阳性胶质细胞的形状，改变基因表达。基因本体富集分析表明，特别是编码参与增殖、分化、迁移和凋亡的蛋白质的基因失调。不同基因的上调和下调通过qPCR和Western印迹分析证实。此外，组蛋白H1减少过氧化氢诱导的细胞死亡的培养motoneurs.Conclusions：综合观察表明，组蛋白H1局部应用于病变部位，提高脊髓损伤后的再生。组蛋白H1在体内和体外的这些有益功能中的一些可以归因于其与携带PSA的神经细胞粘附分子的相互作用。
Background: We have shown that histone H1 is a binding partner for polysialic acid (PSA) and that it improves functional recovery, axon regrowth/sprouting, and target reinnervation after mouse femoral nerve injury.Objective: Here, we analyzed whether histone H1 affects functional recovery, axon regrowth/sprouting, and target reinnervation after spinal cord injury of adult mice. Furthermore, we tested in vitro histone H1's effect on astrocytic gene expression, cell shape and migration as well as on cell survival of cultured motoneurons.Methods: We applied histone H1 to compressed spinal cord and determined functional recovery and number of fibrillary acidic protein (GFAP)- and neuron-glial antigen 2 (NG2)-positive glial cells, which contribute to glial scarring. Histone H1's effect on migration of astrocytes, astrocytic gene expression and motoneuronal survival was determined using scratch-wounded astroglial monolayer cultures, astrocyte cultures for microarray analysis, and motoneuron cell culture under oxidative stress conditions, respectively.Results: Histone H1 application improves locomotor functions and enhances monoaminergic and cholinergic reinnervation of the spinal cord. Expression levels of GFAP and NG2 around the lesion site were decreased in histone H1-treated mice relative to vehicle-treated mice six weeks after injury. Histone H1 reduced astrocytic migration, changed the shape of GFAP- and NG2-positive glial cells and altered gene expression. Gene ontology enrichment analysis indicated that in particular genes coding for proteins involved in proliferation, differentiation, migration and apoptosis are dysregulated. The up- and down-regulation of distinct genes was confirmed by qPCR and Western blot analysis. Moreover, histone H1 reduced hydrogen peroxide-induced cell death of cultured motoneurons.Conclusions: The combined observations indicate that histone H1 locally applied to the lesion site, improves regeneration after spinal cord injury. Some of these beneficial functions of histone H1 in vivo and in vitro can be attributed to its interaction with PSA-carrying neural cell adhesion molecule.