Comparing axon regeneration in male and female mice after peripheral nerve injury

2021 ◽  
Author(s):  
Eun‐Hae Jang ◽  
Yun‐Hee Bae ◽  
Eun Mo Yang ◽  
Yunho Gim ◽  
Hyun‐Jun Suh ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Male And Female ◽  
Female Mice

scholarly journals Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury

2021 ◽  
Vol 22 (13) ◽  
pp. 7217
Author(s):  
Arthur W. English ◽  
Ken Berglund ◽  
Dario Carrasco ◽  
Katharina Goebel ◽  
Robert E. Gross ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Viral Vectors ◽  
Axon Regeneration ◽  
Intraperitoneal Administration ◽  
Experimental Therapy ◽  
Promising Therapeutic Approach ◽  
Compound Muscle Action Potentials

Functional recovery after peripheral nerve injury (PNI) is poor, mainly due to the slow and incomplete regeneration of injured axons. Experimental therapies that increase the excitability of the injured axons have proven remarkably successful in promoting regeneration, but their clinical applicability has been limited. Bioluminescent optogenetics (BL-OG) uses luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate. Excitatory luminopsins were expressed in motoneurons of transgenic mice and in wildtype mice transduced with adeno-associated viral vectors. Intraperitoneal administration of coelenterazine (CTZ), a known luciferase substrate, generated intense bioluminescence in peripheral axons. This bioluminescence increased motoneuron excitability. A single administration of CTZ immediately after sciatic nerve transection and repair markedly enhanced motor axon regeneration. Compound muscle action potentials were 3–4 times larger than controls by 4 weeks after injury. The results observed with transgenic mice were comparable to those of mice in which the luminopsin was expressed using viral vectors. Significantly more motoneurons had successfully reinnervated muscle targets four weeks after nerve injury in BL-OG treated mice than in controls. Bioluminescent optogenetics is a promising therapeutic approach to enhancing axon regeneration after PNI.

scholarly journals Intracellular phospholipase A2 group IVA and group VIA play important roles in Wallerian degeneration and axon regeneration after peripheral nerve injury

Brain ◽  
2008 ◽  
Vol 131 (10) ◽  
pp. 2620-2631 ◽  
Author(s):  
Rubèn López-Vales ◽  
Xavier Navarro ◽  
Takao Shimizu ◽  
Constantinos Baskakis ◽  
George Kokotos ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Phospholipase A2 ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Wallerian Degeneration ◽  
Axon Regeneration ◽  
Group Iva

scholarly journals Characterizing Sex Differences in Depressive-Like Behavior and Glial Brain Cell Changes Following Peripheral Nerve Injury in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Vassilia Michailidis ◽  
Navdeep K. Lidhar ◽  
Chulmin Cho ◽  
Loren J. Martin
Keyword(s):  
Chronic Pain ◽  
Nucleus Accumbens ◽  
Peripheral Nerve ◽  
Glial Cell ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Cell Activation ◽  
Pain Processing ◽  
Male And Female ◽  
Cell Changes

Chronic pain and depression are intimately linked; the combination of the two leads to higher health care costs, lower quality of life, and worse treatment outcomes with both conditions exhibiting higher prevalence among women. In the current study, we examined the development of depressive-like behavior in male and female mice using the spared nerve injury (SNI) model of neuropathic pain. Males displayed increased immobility on the forced-swim test – a measure of depressive-like behavior – 2 weeks following injury, while females developed depressive-like behavior at 3-week. Since the pathogenesis of chronic pain and depression may involve overlapping mechanisms including the activation of microglial cells, we explored glial cell changes in brain regions associated with pain processing and affect. Immunohistochemical analyses revealed that microglial cells were more numerous in female SNI mice in the contralateral ventral anterior cingulate cortex (ACC), a brain region important for pain processing and affect behavior, 2-week following surgery. Microglial cell activation was not different between any of the groups for the dorsal ACC or nucleus accumbens. Analysis of astrocyte density did not reveal any significant changes in glial fibrillary acidic protein (GFAP) staining in the ACC or nucleus accumbens. Overall, the current study characterized peripheral nerve injury induced depression-like behavior in male and female mice, which may be associated with different patterns of glial cell activation in regions important for pain processing and affect.

scholarly journals Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury

2020 ◽  
Vol 16 ◽  
pp. 174480692097191
Author(s):  
Yuanyuan Jia ◽  
Ming Zhang ◽  
Pei Li ◽  
Wenbo Tang ◽  
Yao Liu ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Sciatic Nerve Injury ◽  
Sciatic Nerve Crush ◽  
Non Coding Rnas

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4–L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.

scholarly journals Topoisomerase I inhibition and peripheral nerve injury induce DNA breaks and ATF3-associated axon regeneration in sensory neurons

Cell Reports ◽  
2021 ◽  
Vol 36 (10) ◽  
pp. 109666
Author(s):  
Yung-Chih Cheng ◽  
Andrew Snavely ◽  
Lee B. Barrett ◽  
Xuefei Zhang ◽  
Crystal Herman ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Sensory Neurons ◽  
Peripheral Nerve Injury ◽  
Topoisomerase I ◽  
Axon Regeneration ◽  
Dna Breaks

scholarly journals The long noncoding RNA Arrl1 inhibits neurite outgrowth by functioning as a competing endogenous RNA during neuronal regeneration in rats

2020 ◽  
Vol 295 (25) ◽  
pp. 8374-8386 ◽  
Author(s):  
Dong Wang ◽  
Yanping Chen ◽  
Mingwen Liu ◽  
Qianqian Cao ◽  
Qihui Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Neurite Outgrowth ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Peripheral Nerve Injury ◽  
Axon Regeneration ◽  
Neuronal Regeneration ◽  
Competing Endogenous Rna ◽  
Drg Neurons

The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq–based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.

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