Cysteine- and glycine-rich protein 1a is involved in spinal cord regeneration in adult zebrafish.

Cysteine- and glycine-rich protein 1a is involved in spinal cord regeneration in adult zebrafish.
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DOI:
10.1111/j.1460-9568.2011.07958.x
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发表时间:
2012-02
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Schachner M
Schachner M
中科院分区:
其他
文献类型:
--
作者:
Ma L;Yu YM;Guo Y;Hart RP;Schachner M

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与哺乳动物相比,成年斑马鱼在脊髓损伤(SCI)后具有再生下行轴突和获得运动恢复的能力。在斑马鱼中,成功脊髓再生的决定性因素是一些神经元在再生期间通过(重新)表达生长相关基因来再生其轴突的固有能力。内侧纵束核(NMLF)是脊髓损伤后具有再生反应能力的核团之一。使用激光捕获显微切割NMLF的微阵列分析,我们表明,半胱氨酸和甘氨酸丰富的蛋白1(CRP1,由斑马鱼中的csrp1a基因编码),其功能在神经系统中很大程度上是未知的,在SCI后上调。原位杂交证实了脊髓损伤后轴突生长期神经元中csrp1a的上调,不仅在NMLF中,而且在其他能够再生的核中,如中间网状结构(IMRF)和上级网状结构(SRF)。脊髓损伤后3天,再生核中的csrp1a开始上调,并持续到损伤后21天,这是研究的最长时间点。与对照吗啉相比,使用两种不同的反义吗啉代寡核苷酸在体内敲低CRP 1损害轴突再生和运动恢复,表明CRP 1上调是成年斑马鱼受损神经元先天再生能力的重要组成部分。总之,这项研究是第一个证明斑马鱼脊髓再生需要CRP1的研究。
In contrast to mammals, adult zebrafish have the ability to regrow descending axons and gain locomotor recovery after spinal cord injury (SCI). In zebrafish, a decisive factor for successful spinal cord regeneration is the inherent ability of some neurons to regrow their axons via (re)expressing growth associated genes during the regeneration period. The nucleus of the medial longitudinal fascicle (NMLF) is one of the nuclei capable of regenerative response after SCI. Using microarray analysis with laser capture microdissected NMLF, we show that cysteine and glycine-rich protein 1 (CRP1, encoded by the csrp1a gene in zebrafish), whose function is largely unknown in the nervous system, was upregulated after SCI. In situ hybridization confirmed the upregulation of csrp1a in neurons during the axon growth phase after SCI, not only in the NMLF, but also in other nuclei capable of regeneration, such as the intermediate reticular formation (IMRF) and the superior reticular formation (SRF). The upregulation of csrp1a in regenerating nuclei started at 3 days after SCI and continued to 21 days post-injury, the longest time point studied. In vivo knockdown of CRP1 using two different anti-sense morpholino oligonucleotides impaired axon regeneration and locomotor recovery when compared to a control morpholino, demonstrating that CRP1 upregulation is an important part of the innate regeneration capability in injured neurons of adult zebrafish. Together, this study is the first to demonstrate the requirement of CRP1 for zebrafish spinal cord regeneration.
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