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Expression Profile of Flotillin-2 and Its Pathophysiological Role After Spinal Cord Injury

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Abstract

Some receptors that block axonal regeneration or promote cell death after spinal cord injury (SCI) are localized in membrane rafts. Flotillin-2 (Flot-2) is an essential protein associated with the formation of these domains and the clustering of membranal proteins, which may have signaling activities. Our hypothesis is that trauma will change Flot-2 expression and interference of this lipid raft marker will promote functional locomotor recovery after SCI. Analyses were conducted to determine the spatiotemporal profile of Flot-2 expression in adult rats after SCI, using the MASCIS impactor device. Immunoblots showed that SCI produced a significant decrease in the level of Flot-2 at 2 days post-injury (DPI) that increased until 28 DPI. Confocal microscopy revealed Flot-2 expression in neurons, reactive astrocytes and oligodendrocytes specifically associated to myelin structures near or close to the axons of the cord. In the open field test and grid walking assays, to monitor locomotor recovery of injured rats infused intrathecally with Flot-2 antisense oligonucleotides for 28 days showed significant behavioral improvement at 14, 21 and 28 DPI. These findings suggest that Flot-2 has a role in the nonpermissive environment that blocks locomotor recovery after SCI by clustering unfavorable proteins in membrane rafts.

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Acknowledgements

Special thanks to the Experimental Surgery Facilities, the Animal Resource Center, the MBRS/SCORE Molecular Facilities and the RCMI Image Center at the UPR Medical Sciences Campus for the use of their facilities. This research project is in partial fulfillment of Mr. José M. Santiago’s doctoral dissertation. This work was supported by grants MBRS-RISE Program (R25-GM068138), MBRS/SCORE (S06-GM008224), NIH/NINDS (39405), M-RISP (532851), RCMI (G12RR03051) and the Associate Deanship of Biomedical Sciences and Graduate Studies of the UPR School of Medicine. Editorial support was provided by Dr. Mary Helen Mays, Puerto Rico Clinical and Translational Research Consortium, funded by the National Center for Research Resources (NCRR) (1U54RR026139-01A1), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.”

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Authors and Affiliations

  1. Department of Natural Sciences, University of Puerto Rico Carolina Campus, Carolina, 00984, Puerto Rico

    José M. Santiago

  2. Department of Physiology, University of Puerto Rico School of Medicine, PO Box 365067, San Juan, 00936-5067, Puerto Rico

    Aranza I. Torrado, Luz C. Arocho, Odrick R. Rosas, Ana E. Rodríguez, Franchesca König Toro, Iris K. Salgado, Yaría Arroyo Torres, Walter I. Silva & Jorge D. Miranda

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  1. José M. Santiago
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Correspondence to Jorge D. Miranda.

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Santiago, J.M., Torrado, A.I., Arocho, L.C. et al. Expression Profile of Flotillin-2 and Its Pathophysiological Role After Spinal Cord Injury. J Mol Neurosci 49, 347–359 (2013). https://doi.org/10.1007/s12031-012-9873-7

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  • DOI: https://doi.org/10.1007/s12031-012-9873-7

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