Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin‐1 and ErbB receptors

Nicolino, S.; Panetto, A.; Raimondo, Stefania; Gambarotta, Giovanna; Guzzini, Matteo; Fornaro, Michele; Battiston, Bruno; Tos, Pierluigi; Geuna, Stefano; Perroteau, Isabelle

doi:10.1002/micr.20636

Cited by 22 publications

(17 citation statements)

References 41 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While regulation of Nrg1 receptors ErbB2 and ErbB3 are essential to peripheral nerve responses to injury (Mukhatyar et al, 2013; Nicolino et al, 2009), the probes for ErbB2 and ErbB3 were not present on Illumina Mouse Ref8-v2 chips, precluding the ability to address regulation of ErbB2 and ErbB3 genes in these studies.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

Freidin

Asche-Godin

Abrams

2015

Experimental Neurology

View full text Add to dashboard Cite

X-linked Charcot–Marie–Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the human gene for Connexin32 (Cx32). This present study uses Ilumina Ref8-v2 BeadArray to examine the expression profiles of injured and uninjured sciatic nerves at 5, 7, and 14 days post-crush injury (dpi) from Wild Type (WT) and Cx32-knockout (Cx32KO) mice to identify the genes and signaling pathways that are dysregulated in the absence of Schwann cell Cx32. Given the assumption that loss of Schwann cell Cx32 disrupts the regeneration and maintenance of myelinated nerve leading to a demyelinating neuropathy in CMT1X, we initially hypothesized that nerve crush injury would result in significant increases in differential gene expression in Cx32KO mice relative to WT nerves. However, microarray analysis revealed a striking collapse in the number of differentially expressed genes at 5 and 7 dpi in Cx32KO nerves relative to WT, while uninjured and 14dpi time points showed large numbers of differentially regulated genes. Further comparisons within each genotype showed limited changes in Cx32KO gene expression following crush injury when compared to uninjured Cx32KO nerves. By contrast, WT nerves exhibited robust changes in gene expression at 5 and 7dpi with no significant differences in gene expression by 14dpi relative to uninjured WT nerve samples. Taken together, these data suggest the gene expression profile in uninjured Cx32KO sciatic nerve strongly resembles that of a WT nerve following injury and that loss of Schwann cell Cx32 leads to a basal state of gene expression similar to that of an injured WT nerve. These findings support a role for Cx32 in non-myelinating and regenerating populations of Schwann cells in normal axonal maintenance in re-myelination, and regeneration of peripheral nerve following injury. Disruption of Schwann cell-axonal communication in CMT1X may cause dysregulation of signaling pathways that are essential for the maintenance of intact myelinated peripheral nerves and to establish the necessary conditions for successful regeneration and remyelination following nerve injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

Freidin

Asche-Godin

Abrams

2015

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…A possible alternative to the nerve graft is the tubulization technique . Particularly the muscle vein combined graft has already been successfully used in the clinical practise, with good results for sensory recovery and preserving the donor nerves, although less favorable results were observed for motor function and for substance loss more than 3 cm .…”

Section: Discussionmentioning

confidence: 99%

The amnion muscle combined graft (AMCG) conduits: A new alternative in the repair of wide substance loss of peripheral nerves

et al. 2014

Self Cite

View full text Add to dashboard Cite

The use of autologous sural nerve grafts is still the current gold standard for the repair of peripheral nerve injuries with wide substance losses, but with a poor rate of functional recovery after repair of mixed and motor nerves, a limited donor nerve supply, and morbidity of donor site. At present, tubulization through the muscle vein combined graft, is a viable alternative to the nerve autografts and certainly is a matter of tissue engineering still open to continuous development, although this technique is currently limited to a critical gap of 3 cm with less favorable results for motor function recovery. In this report, we present a completely new tubulization method, the amnion muscle combined graft (AMCG) technique, that consists in the combination of the human amniotic membrane hollow conduit with autologous skel-etal muscle fragments for repairing the substance loss of peripheral nerves and recover both sensory and motor functions. In a series of five patients with loss of substance of the median nerve ranging 3-5 cm at the wrist, excellent results graded as S4 in two cases, S31 in two cases, and S3 in one case; M4 in four cases and M3 in one case were achieved. No iatrogenic damage due to withdrawal of a healthy nerve from donor site was observed. This technique allows to repair extensive loss of substance up to 5 cm with a good sensory and motor recovery. The AMCG thus may be considered a reasonable alternative to traditional nerve autograft in selected clinical condi-tions. V C ,

show abstract

Section: The Expression Of Nrg1 Isoforms and Their Receptors Changes Fomentioning

confidence: 96%

“…NRG1 expression was quantified in the target muscle flexor digitorum following denervation by median nerve transection. Denervation was found to dramatically increase the levels of NRG1α isoforms and erbB2 and erbB3 receptors in the muscle and on re-innervation of the muscle the levels decreased [85].The expression of NRG1 isoforms and erbB receptors is clearly dysregulated following peripheral nerve injury. This finding, along with the role of NRG1 in axoglial signaling during development, has led to the hypothesis that NRG1 may play a role in the response to nerve injury.…”

mentioning

confidence: 99%

The Role of Neuregulin-1 In the Response To Nerve Injury

Fricker

Bennett

2011

Future Neurol.

View full text Add to dashboard Cite

Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors on Schwann cells, regulates multiple phases of their development. In adulthood, NRG1 is dispensable for the maintenance of the myelin sheath; however, this factor is required for both axon regeneration and remyelination following nerve injury. The outcome of NRG1 signaling depends on interactions with other pathways within Schwann cells such as Notch, integrin and cAMP signaling. In certain circumstances, this signaling pathway may be maladaptive; for instance, direct binding of Mycobacterium leprae onto erbB2 receptors produces excessive activation and can actually promote demyelination. Attempts to modulate this pathway in order to promote nerve repair will therefore need to give consideration to the exact isoform used, as well as how it is processed and the context in which it is presented to the Schwann cell. Keywordsneuregulin-1; neuropathy; peripheral nerve injury; regeneration; remyelination; repair; Schwann cell Peripheral nerve injury causes significant morbidity and reduced quality of life as a consequence of weakness, sensory loss and neuropathic pain. In total, 6% of the elderly population suffer from peripheral neuropathy [1], which can be caused by metabolic diseases such as diabetes, inherited genetic disorders such as Charcot-Marie-Tooth disease, infectious and inflammatory disorders including Guillan-Barré syndrome and traumatic injury to the nerve (which alone effects up to 300,000 people in Europe per year [1,2]). In contrast to the CNS, peripheral nerves have a significant regenerative capacity [3]; however, in patients, regeneration and the clinical outcome are often poor. Axons regenerate at a rate of approximately 1 mm per day, depending on the site of the lesion. There may be a delay of months if not years before the target zone is re-innervated, and by this time, the target organ and supporting cells may have irreversibly changed, becoming much less receptive to reinnervation. The current approaches to peripheral nerve repair following nerve transection are either to surgically suture the nerve or to bridge the gap between the two cut ends. Financial & competing interests disclosureThe authors have no other rel evant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Europe PMC Funders Group NRGs & the PNSNRGs Neuregulins are a family of growth factors en...

show abstract

Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin‐1 and ErbB receptors

Cited by 22 publications

References 41 publications

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

The amnion muscle combined graft (AMCG) conduits: A new alternative in the repair of wide substance loss of peripheral nerves

The Role of Neuregulin-1 In the Response To Nerve Injury

Contact Info

Product

Resources

About