MicroRNA-124 Overexpression in Schwann Cells Promotes Schwann Cell-Astrocyte Integration and Inhibits Glial Scar Formation Ability

Frontiers in Cellular Neuroscience, 2020 · DOI: 10.3389/fncel.2020.00144 · Published: July 2, 2020

Simple Explanation

Schwann cell transplantation is a promising approach for the treatment of spinal cord injury (SCI); however, SC grafts show a low migratory capacity within the astrocytic environment, which inevitably hampers their therapeutic efficacy. The purpose of this study was to explore mechanisms to modify the characteristics of SCs and astrocytes (ASs), as well as to adjust the SC-AS interface to break the SC-AS boundary, thus improving the benefits of SCI treatment. Collectively, these results show that overexpression of miR-124 in SCs promotes SC-AS integration in vitro and may attenuate the capacity of ASs to form glial scars.

Study Duration

Not specified

Participants

Adult female Wistar rats (200–220 g), Postnatal Wistar rats (days 1–3)

Evidence Level

Not specified

Key Findings

1
Overexpressing miR-124 in SCs (miR-124-SCs) signiﬁcantly inhibited gene and protein expression levels of SC-speciﬁc markers, such as GFAP and Krox20.
2
The expression of neurotrophic factors, Bdnf and Nt-3, was up-regulated in miR-124-SCs without affecting their proliferation.
3
Krox20 protein expression was down-regulated in miR-124-SCs, the luciferase assay showed that Krox20 is not a direct target of miR-124.

Research Summary

This study explored mechanisms to modify Schwann cells (SCs) and astrocytes (ASs) characteristics and adjust the SC-AS interface to improve spinal cord injury (SCI) treatment benefits. Overexpression of miR-124 in SCs facilitates SC-AS integration by indirectly down-regulating Krox20 expression and inhibiting the activation of ASs. This study provides novel insights into modifying SCs by overexpressing miR-124 to improve their therapeutic potential in SCI.

Practical Implications

Improved SCI Treatment

Modifying SCs with miR-124 could lead to better integration with astrocytes, potentially improving neural tissue repair after SCI.

Reduced Glial Scarring

The study suggests that miR-124 overexpression may attenuate the capacity of astrocytes to form glial scars, promoting a more permissive environment for regeneration.

Targeted Therapeutic Strategies

Identifying key genes and pathways involved in SC motility and migration could inform the development of targeted therapies to enhance SC transplantation efficacy.

Study Limitations

1
The study primarily focuses on in vitro experiments.
2
The exact mechanisms by which miR-124 indirectly regulates Krox20 and other target genes require further investigation.
3
The long-term effects and safety of miR-124-modified SCs in vivo need to be evaluated.

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