scholarly journals LncRNA BC083743 Promotes the Proliferation of Schwann Cells and Axon Regeneration Through miR-103-3p/BDNF After Sciatic Nerve Crush

2020 ◽  
Vol 79 (10) ◽  
pp. 1100-1114
Author(s):  
Lin Gao ◽  
Aiqin Feng ◽  
Peijian Yue ◽  
Yue Liu ◽  
Qiaoyu Zhou ◽  
...  

Abstract To investigate the underlying mechanism of lncRNA BC083743 in regulating the proliferation of Schwann cells (SCs) and axon regeneration after sciatic nerve crush (SNC), we used a rat model. Sciatic function index and the atrophy ratio of gastrocnemius muscle were evaluated. The relationship among BC083743, miR-103-3p, and brain-derived neurotrophic factor (BDNF) and their regulation mechanism in the repair of SNC were investigated using in vivo and in vitro experiments. The expression changes of BC083743 were positively associated with that of BDNF following SNC, but the expression changes of miR-103-3p were inversely associated with that of BDNF. The SC proliferation and BDNF expression could be promoted by overexpression of BC083743, while they were inhibited by a miR-103-3p mimic. In addition, BC083743 interacted with and regulated miR-103-3p, thereby promoting BDNF expression and SC proliferation. BC083743 overexpression also promoted axon regeneration through miR-103-3p. In vivo experiments also indicated that BC083743 overexpression promoted the repair of SNC. In conclusion, LncRNA BC083743 promotes SC proliferation and the axon regeneration through miR-103-3p/BDNF after SNC.

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Susu Mao ◽  
Tao Huang ◽  
Yuanyuan Chen ◽  
Longxiang Shen ◽  
Shuoshuo Zhou ◽  
...  

Abstract Accumulating evidence suggests that circular RNAs (circRNAs) are abundant and play critical roles in the nervous system. However, their functions in axon regeneration after neuronal injury are unclear. Due to its robust regeneration capacity, peripheral nervous system is ideal for seeking the regulatory circRNAs in axon regeneration. In the present work, we obtained an expression profile of circRNAs in dorsal root ganglions (DRGs) after rat sciatic nerve crush injury by RNA sequencing (RNA-Seq) and found the expression level of circ-Spidr was obviously increased using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, circ-Spidr was proved to be a circular RNA enriched in the cytoplasm of DRG neurons. Through in vitro and in vivo experiments, we determined that down-regulation of circ-Spidr could suppress axon regeneration of DRG neurons after sciatic nerve injury partially through modulating PI3K-Akt signaling pathway. Together, our results reveal a crucial role for circRNAs in regulating axon regeneration after neuronal injury which may further serve as a potential therapeutic avenue for neuronal injury repair.


1979 ◽  
Vol 57 (11) ◽  
pp. 1251-1255
Author(s):  
M. A. Bisby ◽  
C. E. Hilton

A previous study by McLean and co-workers reported that regenerating axons of the rabbit vagus nerve were unable to sustain axonal transport in vitro for several months after nerve injury. In contrast, we found that sensory axons of the rat sciatic nerve were able to transport 3H-labeled protein into their regenerating portions distal to the site of injury within a week after injury when placed in vitro. Transport in vitro was not significantly less than transport in axons maintained in vivo for the same period. Transport occurred in the medium that was used by the McLean group, but was significantly reduced in calcium-free medium. When axon regeneration was delared, only small amounts of activity were present in the nerve distal to the site of injury, showing that labeled protein normally present in that part of the nerve was associated with axons and was not a result of local precursor uptake by nonneural elements in the sciatic nerve. We were not able to explain the failure of McLean and co-workers to demonstrate transport in vitro in regenerating vagus nerve, but we conclude that there is no general peculiarity of growing axons that makes them unable to sustain transport in vitro.


2012 ◽  
Vol 49 (3) ◽  
pp. 512-522 ◽  
Author(s):  
Hao Wu ◽  
Yonghua Liu ◽  
Yuan Zhou ◽  
Long Long ◽  
Xinghai Cheng ◽  
...  

2002 ◽  
Vol 159 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Caroline Pot ◽  
Marjo Simonen ◽  
Oliver Weinmann ◽  
Lisa Schnell ◽  
Franziska Christ ◽  
...  

Înjured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration.


2013 ◽  
Vol 44 (4) ◽  
pp. 391-399 ◽  
Author(s):  
Jianhua Cao ◽  
Xinghai Cheng ◽  
Zhengming Zhou ◽  
Huiqing Sun ◽  
Feng Zhou ◽  
...  

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Erin-Mai F. Lim ◽  
Vahid Hoghooghi ◽  
Kathleen M. Hagen ◽  
Kunal Kapoor ◽  
Ariana Frederick ◽  
...  

Abstract Background Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury. Methods Sciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab−/−) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting. Results We report that (1) more pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab−/− mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro. Conclusions CRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.


2010 ◽  
Vol 104 (2) ◽  
pp. 695-703 ◽  
Author(s):  
Joshua M. Britt ◽  
Jacqueline R. Kane ◽  
Christopher S. Spaeth ◽  
Aleksej Zuzek ◽  
Garrett L. Robinson ◽  
...  

The inability to rapidly (within minutes to hours) improve behavioral function after severance of peripheral nervous system axons is an ongoing clinical problem. We have previously reported that polyethylene glycol (PEG) can rapidly restore axonal integrity (PEG-fusion) between proximal and distal segments of cut- and crush-severed rat axons in vitro and in vivo. We now report that PEG-fusion not only reestablishes the integrity of crush-severed rat sciatic axons as measured by the restored conduction of compound action potentials (CAPs) and the intraaxonal diffusion of fluorescent dye across the lesion site, but also produces more rapid recovery of appropriate hindlimb motor behaviors. Improvement in recovery occurred during the first few postoperative weeks for the foot fault (FF) asymmetry test and between week 2 and week 3 for the Sciatic Functional Index (SFI) based on analysis of footprints. That is, the FF test was the more sensitive indicator of early behavioral recovery, showing significant postoperative improvement of motor behavior in PEG-treated animals at 24–48 h. In contrast, the SFI more sensitively measured longer-term postoperative behavioral recovery and deficits at 4–8 wk, perhaps reflecting the development of fine (distal) motor control. These and other data show that PEG-fusion not only rapidly restores physiological and morphological axonal continuity, but also more quickly improves behavioral recovery.


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