The Cancer Drug Tamoxifen: A Potential Therapeutic Treatment for Spinal Cord Injury

被引:32
作者
Guptarak, Jutatip [1 ]
Wiktorowicz, John E. [1 ]
Sadygov, Rovshan G. [1 ]
Zivadinovic, Dragoslava [1 ]
Paulucci-Holthauzen, Adriana A. [1 ]
Vergara, Leoncio [2 ]
Nesic, Olivera [1 ,3 ]
机构
[1] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Ctr Biomed Engn, Galveston, TX 77555 USA
[3] Texas Tech Univ, Dept Med Educ, Paul L Foster Sch Med, El Paso, TX 79905 USA
关键词
ESTROGEN-RECEPTOR MODULATORS; PROTEIN-KINASE-C; GENE-EXPRESSION; GLIAL-CELLS; NUCLEAR RECEPTORS; BODY-WEIGHT; FOOD-INTAKE; RATS; BRAIN; AQUAPORIN-4;
D O I
10.1089/neu.2013.3108
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Tamoxifen (TMX) is a selective estrogen receptor modulator that can mimic the neuroprotective effects of estrogen but lacks its systemic adverse effects. We found that TMX (1 mg/day) significantly improved the motor recovery of partially paralyzed hind limbs of male adult rats with thoracic spinal cord injury (SCI), thus indicating a translational potential for this cancer medication given its clinical safety and applicability and the lack of currently available treatments for SCI. To shed light on the mechanisms underlying the beneficial effects of TMX for SCI, we used proteomic analyses, Western blots and histological assays, which showed that TMX treatment spared mature oligodendrocytes/increased myelin levels and altered reactive astrocytes, including the upregulation of the water channels aquaporin 4 (AQP4), a novel finding. AQP4 increases in TMX-Treated SCI rats were associated with smaller fluid-filled cavities with borders consisting of densely packed AQP4-expressing astrocytes that closely resemble the organization of normal glia limitans externa (in contrast to large cavities in control SCI rats that lacked glia limitans-like borders and contained reactive glial cells). Based on our findings, we propose that TMX is a promising candidate for the therapeutic treatment of SCI and a possible intervention for other neuropathological conditions associated with demyelination and AQP4 dysfunction. © Copyright 2014, Mary Ann Liebert, Inc. 2014.
引用
收藏
页码:268 / 283
页数:16
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