Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract

Spinal and bulbar muscular atrophy (SBMA) is associated with an abnormal ex pansion of the (CAG)(n) repeat in the androgen receptor (AR) gene. Similar mutations have been reported in other proteins that cause neurodegenerative disorders. The GAG-coded elongated polyglutamine (polyGln) tracts induce t he formation of neuronal intracellular aggregates. We have produced a model to study the effects of potentially 'neurotoxic' aggregates in SBMA using immortalized motoneuronal cells (NSC34) transfected with AR containing poly Gln repeats of different sizes [(AR.Q(n = 0, 23 or 46)]. Using chimeras of AR.Q(n) and the green fluorescent protein (GFP), we have shown that aggrega te formation occurs when the polyGln tract is elongated and AR is activated by androgens, In NSC34 cells co-expressing the AR with the polyGln of path ological length (AR,Q46) and the GFP we have noted the presence of several dystrophic neurites, Cell viability analyses have shown a reduced growth/su rvival rate in NSC34 expressing the AR,Q46, whereas testosterone treatment partially counteracted both cell death and the formation of dystrophic neur ites, These observations indicate the lack of correlation between aggregate formation and cell survival, and suggest that neuronal degeneration in SBM A might be secondary to axonal/dendritic insults.