Schwann cell‐specific <scp>RhoA</scp> knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation

Liu, Jingmin; Ma, Xiaokun; Hu, Xiaofang; Wen, Jinkun; Zhang, Haowen; Xu, Jikai; He, Ye; Wang, Xianghai; Guo, Jiasong

doi:10.1002/glia.24365

Cited by 12 publications

(4 citation statements)

References 43 publications

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“…The survival of central facial motoneurons was crucial for peripheral nerve healing. The most effective neurotrophic factor for stimulating neuronal growth in vitro is GDNF, 24 but it is only sparingly produced in neuronal tissues. Instead, the majority of GDNF is produced and secreted by peripheral target tissues that are innervated by it, and it is then transported retrogradely to the motoneurons along the axon by uptaking through the nerve endings.…”

Section: Discussionmentioning

confidence: 99%

Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway

Fei,

Chen,

Song

et al. 2023

The FASEB Journal

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Facial nerve regeneration still lacks a well‐defined and practical clinical intervention. The survival of central facial motoneuron is a critical component in the successful peripheral facial nerve regeneration. Endogenous GDNF is vital for facial nerve regeneration according to earlier investigations. Nevertheless, the low endogenous GDNF level makes it challenging to achieve therapeutic benefits. Thus, we crushed the main trunk of facial nerve in SD rats to provide a model of peripheral facial paralysis, and we administered exogenous GDNF and Rapa treatments. We observed changes in the animal behavior scores, the morphology of facial nerve and buccinator muscle, the electrophysiological of facial nerve, and the expression of GDNF, GAP‐43, and PI3K/AKT/mTOR signaling pathway‐related molecules in the facial motoneurons. We discovered that GDNF could boost axon regeneration, hasten the recovery of facial paralysis symptoms and nerve conduction function, and increase the expression of GDNF, GAP‐43, and PI3K/AKT/mTOR signaling pathway‐related molecules in the central facial motoneurons. Therefore, exogenous GDNF injection into the buccinator muscle can enhance facial nerve regeneration following crushing injury and protect facial neurons via the PI3K/AKT/mTOR signaling pathway. This will offer a fresh perspective and theoretical foundation for the management of clinical facial nerve regeneration.

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Section: Discussionmentioning

confidence: 99%

Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway

Fei,

Chen,

Song

et al. 2023

The FASEB Journal

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“…One key effector in the modulation of the myelinating state of SCs is the inhibition of the GTPase protein RhoA. RhoA reorganizes the actin cytoskeleton in myelinating SCs through interactions with actin-binding proteins Cofilin1 and myosin-II, contributing to SC reprogramming ( Wen et al, 2018 ; Liu et al, 2023 ). Moreover, RhoA indirectly activates the JNK/c-Jun pathway, regulating the transcription of myelin-related genes in SCs during the reprogramming.…”

Section: Player Cells and Intracellular Signaling Pathways In Periphe...mentioning

confidence: 99%

Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration

Izhiman,

Esfandiari

2024

Front. Cell. Neurosci.

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Peripheral nerve injuries lead to significant morbidity and adversely affect quality of life. The peripheral nervous system harbors the unique trait of autonomous regeneration; however, achieving successful regeneration remains uncertain. Research continues to augment and expedite successful peripheral nerve recovery, offering promising strategies for promoting peripheral nerve regeneration (PNR). These include leveraging extracellular vesicle (EV) communication and harnessing cellular activation through electrical and mechanical stimulation. Small extracellular vesicles (sEVs), 30–150 nm in diameter, play a pivotal role in regulating intercellular communication within the regenerative cascade, specifically among nerve cells, Schwann cells, macrophages, and fibroblasts. Furthermore, the utilization of exogenous stimuli, including electrical stimulation (ES), ultrasound stimulation (US), and extracorporeal shock wave therapy (ESWT), offers remarkable advantages in accelerating and augmenting PNR. Moreover, the application of mechanical and electrical stimuli can potentially affect the biogenesis and secretion of sEVs, consequently leading to potential improvements in PNR. In this review article, we comprehensively delve into the intricacies of cell-to-cell communication facilitated by sEVs and the key regulatory signaling pathways governing PNR. Additionally, we investigated the broad-ranging impacts of ES, US, and ESWT on PNR.

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“…Myelin-specific miR-23a/b cluster KO mice were generated by crossbreeding Plp cre-driver mice (Cyagen, Santa Clara, CA, USA) [20] with miR-23a/b clusterfloxed mice on a C57BL6/J background [18,21]. In this study, genetically modified Plp Cre ERT2 ;miR-23a/b cluster mice-a model designed for tamoxifen-induced gene KO-were used, allowing for controlled manipulation of gene expression during specific developmental stages [22,23]. Mice were individually housed under controlled conditions, including a 12 h light/dark cycle, with room temperature maintained at 23 ± 1 • C and humidity levels between 40 and 60%.…”

Section: Animals and Genotypingmentioning

confidence: 99%

Myelin-Specific microRNA-23a/b Cluster Deletion Inhibits Myelination in the Central Nervous System during Postnatal Growth and Aging

Ishibashi,

Kamei,

Tsuchikawa

et al. 2024

Genes

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Microribonucleic acids (miRNAs) comprising miR-23a/b clusters, specifically miR-23a and miR-27a, are recognized for their divergent roles in myelination within the central nervous system. However, cluster-specific miRNA functions remain controversial as miRNAs within the same cluster have been suggested to function complementarily. This study aims to clarify the role of miR-23a/b clusters in myelination using mice with a miR-23a/b cluster deletion (KO mice), specifically in myelin expressing proteolipid protein (PLP). Inducible conditional KO mice were generated by crossing miR-23a/b clusterflox/flox mice with PlpCre-ERT2 mice; the offspring were injected with tamoxifen at 10 days or 10 weeks of age to induce a myelin-specific miR-23a/b cluster deletion. Evaluation was performed at 10 weeks or 12 months of age and compared with control mice that were not treated with tamoxifen. KO mice exhibit impaired motor function and hypoplastic myelin sheaths in the brain and spinal cord at 10 weeks and 12 months of age. Simultaneously, significant decreases in myelin basic protein (MBP) and PLP expression occur in KO mice. The percentages of oligodendrocyte precursors and mature oligodendrocytes are consistent between the KO and control mice. However, the proportion of oligodendrocytes expressing MBP is significantly lower in KO mice. Moreover, changes in protein expression occur in KO mice, with increased leucine zipper-like transcriptional regulator 1 expression, decreased R-RAS expression, and decreased phosphorylation of extracellular signal-regulated kinases. These findings highlight the significant influence of miR-23a/b clusters on myelination during postnatal growth and aging.

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Schwann cell‐specific RhoA knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation

Cited by 12 publications

References 43 publications

Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway

Exogenous GDNF promotes peripheral facial nerve regeneration in rats through the PI3K/AKT/mTOR signaling pathway

Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration

Myelin-Specific microRNA-23a/b Cluster Deletion Inhibits Myelination in the Central Nervous System during Postnatal Growth and Aging

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