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Caveolin‐1 regulates neuronal regeneration in peripheral nerve crush injury via regulation of Schwann cell function
Author(s) -
Garcia Selma Dee,
Dolkas Jennifer,
Shubayev Igor,
Kellerhals Sarah Elizabeth,
Schilling Jan M,
Shubayev Veronica I,
Patel Hemal H,
Kim Youngsoon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1142.8
Subject(s) - schwann cell , microbiology and biotechnology , regeneration (biology) , peripheral nerve injury , crush injury , nerve injury , biology , neuroscience , chemistry , medicine , surgery
Peripheral nerve damage occurs in a variety of settings leading to loss of motor function and potential neuropathic pain. Peripheral nerve injury involves complex changes in Schwann cell signaling and metabolism that ultimately lead to regulation of nerve regeneration, though these mechanisms are poorly understood. Caveolins (Cav) are scaffolding proteins that exist in lipid rafts and regulate a myriad of signal transduction. We hypothesized that Cav is critical to Schwann cell response following nerve injury. Knockdown of Cav‐1 slows the speed of axonal regeneration following nerve crush injury. We also observed increased extracellular regulated kinase 1/2 phosphorylation and cell mitosis in Cav‐1 KO nerves compared to wild‐type following injury. Myelin debris clearance and macrophage content declined in Cav‐1 KO nerves. Electron microscopy revealed loss of Schwann cell mitochondrial in cells distal to the crush site. JS1 Schwann cells showed upregulated mitochondrial function via measurement of ATP synthesis and mitochondrial respiration using Seahorse Metabolic Flux Analyzer when Cav‐1 was upregualted. Our studies suggest that loss of Cav‐1 leads to compromised Schwann cell function leading to diminished nerve regeneration following injury and that Cav‐1 targeted to Schwann cells may be a means to positively regulate Schwann cell function in the setting of injury.