Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

Figure 1

Cellular targets and actions of chronic stress mediated by glucocorticoid receptors. This schema depicts some cellular targets and mechanisms that are targeted by glucocorticoids (GCs), whose actions are mediated by glucocorticoid receptors (GR). GCs are secreted under conditions of stress; neuronal damage and brain pathologies are a common consequence of persistently elevated GC secretion. GC can trigger mitochondrial dysfunction and the apoptotic machinery, as well as cell cycle arrest and cell death. In addition, stress/GC may induce neuronal atrophy and synaptic dysfunction/loss by stimulating hyperphosphorylation of the cytoskeletal protein Tau, thus disturbing the integrity of the cytoskeleton and missorting Tau at synapses. Together, these latter events may eventually result in the degradation of synaptic proteins and receptors and consequently, synaptic plasticity. Stress and GC are also established as modulators of microglial activation and neuroinflammatory processes. Lastly, accumulating evidence indicates that stress and GC can influence neuronal structure and function through epigenetic mechanisms.