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TitleGlucocorticoids and neurodegeneration
Author(s)Vyas, Sheela
Rodrigues, Ana João
Silva, Joana Margarida
Tronche, François
Sousa, Nuno
Sotiropoulos, I.
Editor(s)Santulli, Gaetano
Alzheimer‘s disease
Parkinson‘s disease
Issue date2015
PublisherNova Science Publishers
Abstract(s)Glucocorticoids (GCs) exert wide-spread actions in central nervous system ranging from gene transcription, cellular signaling, modulation of synaptic structure and transmission, glial responses to altered neuronal circuitry and behavior through the activation of two steroid hormone receptors, glucocorticoid receptor (NR3C1, GR) and mineralocorticoid receptor (NR3C2, MR). These highly-related receptors exert both genomic and non-genomic actions in the brain, which are context-dependent and essential for adaptive responses to stress resulting in modulations of behavior, learning and memory processes. Thus, GCs through their receptors are implicated in neural plasticity as they modulate the dendritic and synaptic structure of neurons as well as the survival and fate of newly-generated cells (neuro- and glio-genesis) in adult brain. GCs are also important in fetal brain programming as inappropriate variations in their levels during critical developmental periods are suggested to be casually related to the development of brain pathologies and maladaptive responses of hypothalamic-pituitary adrenal (HPA) axis to stress during adulthood. They regulate immune responses in brain, which have important consequences for neuronal survival. In situations of chronic stress and HPA axis dysfunction resulting in chronically high or low GCs levels, a multitude of molecular, structural and functional changes occur in the brain, eventually leading to maladaptive behavior. In fact, clinical studies suggest a causal relation of deregulated GC responses with development of neurodegenerative disorders such as Alzheimer´s (AD) and Parkinson‘s (PD) diseases. AD and PD patients have high levels of circulating cortisol while animal studies suggest that this chronic GC elevation participates in neurodegenerative processes in both AD and PD pathologies. This chapter will focus on the role of HPA axis and GCs on neurodegenerative processes involved in AD and PD pathogenesis.
DescriptionSeries: Endocrinology research and clinical developments
Publisher version
Appears in Collections:ICVS - Livros e Capítulos de Livros

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