Action of glucocorticoids on survival of nerve cells: Promoting neurodegeneration or neuroprotection?

Extensive studies during the past decades provided compelling evidence that glucocorticoids (GCs) have the potential to affect the development, surviv al and death of neurones. These observations, however, reflect paradoxical features of GCs, as they may be critically involved in both neurodegenerati ve and neuroprotective processes. Hence, we first address different aspects of the complex role of GCs in neurodegeneration and neuroprotection, such as concentration dependent actions of GCs on neuronal viability, anatomical diversity of GC-mediated mechanisms in the brain and species and strain di fferences in GC-induced neurodegeneration. Second, the modulatory action of GCs during development and ageing of the central nervous system, as well a s the contribution of altered GC balance to the pathogenesis of neurodegene rative disorders is considered. In addition, we survey recent data as to th e possible mechanisms underlying the neurodegenerative and neuroprotective actions of GCs. As such, two major aspects will be discerned: (j) GC-depend ent offensive events, such as GC-induced inhibition of glucose uptake, incr eased extracellular glutamate concentration and concomitant elevation of in tracellular Ca2+, decrease in GABAergic signalling and regulation of local GC concentrations by 11 beta -hydroxysteroid dehydrogenases; and (ii) GC-re lated cellular defence mechanisms, such as decrease in after-hyperpolarizat ion, increased synthesis and release of neurotrophic factors and lipocortin -1, feedback regulation of Ca2+ currents and induction of antioxidant enzym es. The particular relevance of these mechanisms to the neurodegenerative a nd neuroprotective effects of GCs in the brain is discussed.