Suppr超能文献

脊髓损伤后条件性基因敲除PTEN可增强小鼠皮质脊髓束轴突的再生生长及运动功能恢复。

Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice.

作者信息

Danilov Camelia A, Steward Oswald

机构信息

Reeve-Irvine Research Center, University of California, Irvine School of Medicine, Irvine, CA 92697, USA.

Reeve-Irvine Research Center, University of California, Irvine School of Medicine, Irvine, CA 92697, USA; Department of Anatomy & Neurobiology, University of California, Irvine School of Medicine, Irvine, CA 92697, USA; Department of Neurobiology & Behavior, University of California, Irvine School of Medicine, Irvine, CA 92697, USA; Department of Neurosurgery, University of California Irvine, School of Medicine, Irvine, CA 92697, USA.

出版信息

Exp Neurol. 2015 Apr;266:147-60. doi: 10.1016/j.expneurol.2015.02.012. Epub 2015 Feb 20.

Abstract

Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTEN(loxP/loxP) mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion and into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery.

摘要

先前的研究表明,新生小鼠中磷酸酶和张力蛋白同源物(PTEN)的条件性基因缺失可增强成年小鼠脊髓损伤(SCI)后轴突的再生能力。在此,我们评估了SCI后在成年神经元中删除PTEN是否也有效,以及再生生长增强是否伴随着自主运动功能恢复的增强。PTEN(loxP/loxP)小鼠在颈5(C5)水平接受中度挫伤。一组在感觉运动皮层单侧注射表达CRE的腺相关病毒(AAV-CRE);对照组注射表达绿色荧光蛋白的载体(AAV-GFP)或仅接受损伤(不注射载体)。SCI后14周使用握力计(GSM)和悬挂任务测试前肢功能。通过将微型红宝石BDA注入感觉运动皮层来追踪皮质脊髓束(CST)。SCI后立即前肢抓握能力严重受损,但随时间缓慢恢复。与AAV-GFP组或仅损伤组相比,PTEN缺失小鼠的恢复程度明显更大。BDA束追踪显示,与对照组相比,PTEN缺失组尾段中BDA标记的轴突数量明显更多。此外,在PTEN缺失组中,有丰富的侧支从损伤部位前方的主束延伸到损伤部位的瘢痕组织内和周围。这些结果表明,SCI后不久在成年小鼠中删除PTEN可增强CST轴突的再生生长和前肢运动功能恢复。

相似文献

4
Pten Deletion Promotes Regrowth of Corticospinal Tract Axons 1 Year after Spinal Cord Injury.
J Neurosci. 2015 Jul 1;35(26):9754-63. doi: 10.1523/JNEUROSCI.3637-14.2015.
8
Effects of PTEN and Nogo Codeletion on Corticospinal Axon Sprouting and Regeneration in Mice.
J Neurosci. 2015 Apr 22;35(16):6413-28. doi: 10.1523/JNEUROSCI.4013-14.2015.
10
Modulation of Both Intrinsic and Extrinsic Factors Additively Promotes Rewiring of Corticospinal Circuits after Spinal Cord Injury.
J Neurosci. 2021 Dec 15;41(50):10247-10260. doi: 10.1523/JNEUROSCI.2649-20.2021. Epub 2021 Nov 10.

引用本文的文献

1
Disruption of G3BP1 granules promotes mammalian CNS and PNS axon regeneration.
Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2411811122. doi: 10.1073/pnas.2411811122. Epub 2025 Feb 27.
2
A bibliometric analysis of the top 100 most cited articles on corticospinal tract regeneration from 2004 to 2024.
Front Neurosci. 2025 Jan 28;18:1509850. doi: 10.3389/fnins.2024.1509850. eCollection 2024.
3
Molecular signaling predicts corticospinal axon growth state and muscle response plasticity induced by neuromodulation.
Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2408508121. doi: 10.1073/pnas.2408508121. Epub 2024 Nov 13.
4
Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury.
J Neurosci. 2025 Jan 1;45(1):e1017242024. doi: 10.1523/JNEUROSCI.1017-24.2024.
5
Enhancing m6A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury.
Neural Regen Res. 2025 Jun 1;20(6):1749-1763. doi: 10.4103/NRR.NRR-D-23-01477. Epub 2024 May 13.
6
Pharmacological intervention for chronic phase of spinal cord injury.
Neural Regen Res. 2025 May 1;20(5):1377-1389. doi: 10.4103/NRR.NRR-D-24-00176. Epub 2024 Jun 26.
8
Non-resolving neuroinflammation regulates axon regeneration in chronic spinal cord injury.
bioRxiv. 2024 Apr 24:2024.04.19.590106. doi: 10.1101/2024.04.19.590106.
9
MicroRNA-133b Dysregulation in a Mouse Model of Cervical Contusion Injury.
Int J Mol Sci. 2024 Mar 6;25(5):3058. doi: 10.3390/ijms25053058.
10
Genes in Axonal Regeneration.
Mol Neurobiol. 2024 Oct;61(10):7431-7447. doi: 10.1007/s12035-024-04049-z. Epub 2024 Feb 22.

本文引用的文献

2
The effect of systemic PTEN antagonist peptides on axon growth and functional recovery after spinal cord injury.
Biomaterials. 2014 May;35(16):4610-26. doi: 10.1016/j.biomaterials.2014.02.037. Epub 2014 Mar 12.
3
Short hairpin RNA against PTEN enhances regenerative growth of corticospinal tract axons after spinal cord injury.
J Neurosci. 2013 Sep 25;33(39):15350-61. doi: 10.1523/JNEUROSCI.2510-13.2013.
4
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3.
Nature. 2011 Nov 6;480(7377):372-5. doi: 10.1038/nature10594.
5
Krüppel-like transcription factors in the nervous system: novel players in neurite outgrowth and axon regeneration.
Mol Cell Neurosci. 2011 Aug;47(4):233-43. doi: 10.1016/j.mcn.2011.05.005. Epub 2011 May 24.
6
Negative impact of rAAV2 mediated expression of SOCS3 on the regeneration of adult retinal ganglion cell axons.
Mol Cell Neurosci. 2011 Feb;46(2):507-15. doi: 10.1016/j.mcn.2010.12.003. Epub 2010 Dec 9.
7
PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
Nat Neurosci. 2010 Sep;13(9):1075-81. doi: 10.1038/nn.2603. Epub 2010 Aug 8.
8
MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma.
J Neurosci. 2010 May 19;30(20):6825-37. doi: 10.1523/JNEUROSCI.6239-09.2010.
9
Neuronal intrinsic barriers for axon regeneration in the adult CNS.
Curr Opin Neurobiol. 2010 Aug;20(4):510-8. doi: 10.1016/j.conb.2010.03.013. Epub 2010 Apr 24.
10
SOCS3 deletion promotes optic nerve regeneration in vivo.
Neuron. 2009 Dec 10;64(5):617-23. doi: 10.1016/j.neuron.2009.11.021.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验