Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures

Rosamaria Orlando, Alessandra Caruso, Gemma Molinaro, Marta Motolese, Francesco Matrisciano, Giuseppina Togna, Daniela Melchiorri, Ferdinando Nicoletti, Valeria Bruno

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The use of anabolic-androgenic steroids (AASs) in the world of sport has raised a major concern for the serious, sometimes life-threatening, side effects associated with these drugs. Most of the CNS effects are of psychiatric origin, and whether or not AASs are toxic to neurons is yet unknown. We compared the effect of testosterone with that of the AASs, 19-nortestosterone (nandrolone), stanozolol, and gestrinone, on excitotoxic neuronal death induced by N-methyl-d-aspartate (NMDA) in primary cultures of mouse cortical cells. In the most relevant experiments, steroids were applied to the cultures once daily during the 4 days preceding the NMDA pulse. Under these conditions, testosterone amplified excitotoxic neuronal death only at very high concentrations (10 μM), whereas it was protective at concentrations of 10 nM and inactive at intermediate concentrations. Low concentrations of testosterone became neurotoxic in the presence of the aromatase inhibitors, i.e. anastrozole and aminoglutethimide, suggesting that the intrinsic toxicity of testosterone was counterbalanced by its aromatization into 17β-estradiol. As opposed to testosterone, nortestosterone, stanozolol and gestrinone amplified NMDA toxicity at nanomolar concentrations; their action was insensitive to aromatase inhibitors, but was abrogated by the androgen receptor antagonist, flutamide. None of the AASs were toxic in the absence of NMDA. These data suggest that AASs increase neuronal vulnerability to an excitotoxic insult and may therefore facilitate neuronal death associated with acute or chronic CNS disorders.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalBrain Research
Volume1165
Issue number1
DOIs
StatePublished - Aug 24 2007

Keywords

  • Anabolic steroid
  • Androgen
  • Cortifical culture
  • Estrogen
  • Excitotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures'. Together they form a unique fingerprint.

  • Cite this

    Orlando, R., Caruso, A., Molinaro, G., Motolese, M., Matrisciano, F., Togna, G., Melchiorri, D., Nicoletti, F., & Bruno, V. (2007). Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures. Brain Research, 1165(1), 21-29. https://doi.org/10.1016/j.brainres.2007.06.047