Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration

Abstract

Stress and stress hormones, glucocorticoids (GCs), exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.The work was supported by Grants “PTDC/SAU-NMC/113934/2009,” funded by FCT, Portuguese Foundation for Science and Technology, and project DoIT, Desenvolvimento e Operacionalização da Investigação de Translação (N° do projeto 13853), funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC). In addition, this work was also cofinanced by European Union FP7 Project SwitchBox (Nuno Sousa, Osborne F. X. Almeida) and the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Sheela Vyas acknowledges grant support from Foundation de France, Physiopathology of Parkinson, France Parkinson and ANR Grant “ParkStrim” N° 13-BSV1-0013-02. Work in FT research group was supported by Agence Nationale de la Recherche (TIMMS and StressPsyco) and Fondation pour la Recherche Médicale, Grant no. DEQ20140329552