Schwann cell regulation of axonal regeneration
In the mammalian nervous system, the regenerative capabilities of neurons show regional variability. In the peripheral nervous system (PNS), axons efficiently regenerate after nerve damage associated to the pro-regenerative effect of Schwann cells. In contrast, in the central nervous system the regenerative capability is poor due to both neuronal intrinsic limitations and glial responses that restrict regeneration. Although, axonal regeneration in the periphery show good regenerative capacity in preclinical models, it still represents a clinical problem associated to delayed repair of peripheral nerves, and the negative effects of aging and other conditions, including diabetes, for axonal regeneration and functional recovery. In the lab, we study how Schwann cells reprogramming regulates axonal regeneration after nerve damage, in order to manipulate this response to enhance axonal regeneration.
Longitudinal section of a sciatic nerve, with regenerating axons crossing a surgically repaired region, axons are labelled using an antibody against the protein SCG10.
Schwann cell exosomes enhance axonal regeneration
In the peripheral nervous system, regeneration of injured axons depends on the reprogramming of Schwann cell from a differentiated phenotype into a phenotype known as repair Schwann cells. Our lab was the first to demonstrate that Schwann cell exosomes enhanced axonal regeneration in vitro and in vivo in laboratory animals, an effect we later showed was dependent on the reprogramming of Schwann cells into a repair phenotype, and associated with the loading of specific miRNA into exosomes and their transfer to axons. In addition, we are exploring the effects of aging, chronic denervation and diabetes in Schwann cell reprograming and axonal regeneration, in order to develop interventions to enhance axonal regeneration in these conditions.
People involved
Daniela Rebolledo
Senior Research Assistant
I am a Biochemist from Pontificia Universidad Católica de Chile (PUC) and PhD in Cell and Molecular Biology from the same university. My PhD thesis research was performed at the Physiology and Biophysics department, University of Washington. My research has focused on the physiology of the neuromuscular system and the pathological mechanisms behind neuromuscular disorders of diverse etiology.
Karina Girardi do Carmo
Postdoctoral fellow
Biologist, Ph.D., and MSc in Cell and Molecular Biology from Oswaldo Cruz Foundation (Fiocruz/RJ). Studying age-dependent decline of regenerative capacity in the peripheral nervous system. Mainly focusing on the contribution of metabolic profile of aging Schwann cells in senescence and particularly exploring the epithelial-mesenchymal transition (EMT) like process.
Renata Gallardo
Research Assistant
I studied Medical Technology at the Universidad Mayor acquiring knowledge in histological techniques, immunohistochemistry and immunofluorescence. I am interested in learning more from the world of neurosciences and related pathologies to find new treatments to improve the quality of life in aging.
Related Publications
PUBLICATIONSDataNervous System FxPNS
octubre 7, 2021
c-Jun N-terminal kinase (JNK)-dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling.
Escudero CA, Cabeza C, Moya-Alvarado G, Maloney MT, Flores CM, Wu C, Court FA, Mobley WC, Bronfman FC.
Sci Rep. 2019 Apr 15;9(1):6070. doi: 10.1038/s41598-019-42420-6.
PMID: 30988348
octubre 7, 2021
Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.
Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C.
Nat Cell Biol. 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y. Epub 2019 May 20.
PMID: 31110288
PUBLICATIONSChapterProtocolNervous System FxPNS
octubre 5, 2021
Purification of Exosomes from Primary Schwann Cells, RNA Extraction, and Next-Generation Sequencing of Exosomal RNAs.
De Gregorio C, Díaz P, López-Leal R, Manque P, Court FA.
Methods Mol Biol. 2018;1739:299-315. doi: 10.1007/978-1-4939-7649-2_19.
PMID: 29546715
PUBLICATIONSChapterProtocolNervous System FxPNS
octubre 5, 2021
Teased Fiber Preparation of Myelinated Nerve Fibers from Peripheral Nerves for Vital Dye Staining and Immunofluorescence Analysis.
Catenaccio A, Court FA.
Methods Mol Biol. 2018;1739:329-337. doi: 10.1007/978-1-4939-7649-2_21.
PMID: 29546717
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