The cancer drug tamoxifen

A potential therapeutic treatment for spinal cord injury

Jutatip Guptarak, John E. Wiktorowicz, Rovshan Sadygov, Dragoslava Zivadinovic, Adriana A. Paulucci-Holthauzen, Leoncio Vergara, Olivera Nesic

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)268-283
Number of pages16
JournalJournal of Neurotrauma
Volume31
Issue number3
DOIs
StatePublished - Feb 1 2014

Fingerprint

Tamoxifen
Spinal Cord Injuries
Aquaporin 4
Neuroglia
Pharmaceutical Preparations
Neoplasms
Astrocytes
Therapeutics
Selective Estrogen Receptor Modulators
Thoracic Injuries
Aquaporins
Oligodendroglia
Demyelinating Diseases
Neuroprotective Agents
Myelin Sheath
Proteomics
Estrogens
Up-Regulation
Extremities
Western Blotting

Keywords

  • Aqp4
  • myelin
  • proteomics
  • spinal cord injury
  • tamoxifen

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Guptarak, J., Wiktorowicz, J. E., Sadygov, R., Zivadinovic, D., Paulucci-Holthauzen, A. A., Vergara, L., & Nesic, O. (2014). The cancer drug tamoxifen: A potential therapeutic treatment for spinal cord injury. Journal of Neurotrauma, 31(3), 268-283. https://doi.org/10.1089/neu.2013.3108

The cancer drug tamoxifen : A potential therapeutic treatment for spinal cord injury. / Guptarak, Jutatip; Wiktorowicz, John E.; Sadygov, Rovshan; Zivadinovic, Dragoslava; Paulucci-Holthauzen, Adriana A.; Vergara, Leoncio; Nesic, Olivera.

In: Journal of Neurotrauma, Vol. 31, No. 3, 01.02.2014, p. 268-283.

Research output: Contribution to journalArticle

Guptarak, J, Wiktorowicz, JE, Sadygov, R, Zivadinovic, D, Paulucci-Holthauzen, AA, Vergara, L & Nesic, O 2014, 'The cancer drug tamoxifen: A potential therapeutic treatment for spinal cord injury', Journal of Neurotrauma, vol. 31, no. 3, pp. 268-283. https://doi.org/10.1089/neu.2013.3108
Guptarak J, Wiktorowicz JE, Sadygov R, Zivadinovic D, Paulucci-Holthauzen AA, Vergara L et al. The cancer drug tamoxifen: A potential therapeutic treatment for spinal cord injury. Journal of Neurotrauma. 2014 Feb 1;31(3):268-283. https://doi.org/10.1089/neu.2013.3108
Guptarak, Jutatip ; Wiktorowicz, John E. ; Sadygov, Rovshan ; Zivadinovic, Dragoslava ; Paulucci-Holthauzen, Adriana A. ; Vergara, Leoncio ; Nesic, Olivera. / The cancer drug tamoxifen : A potential therapeutic treatment for spinal cord injury. In: Journal of Neurotrauma. 2014 ; Vol. 31, No. 3. pp. 268-283.
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