Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

卷:61

Review

Kalafatakis, Konstantinos¹  Russell, Georgina M.¹  Zarros, Apostolos²  Lightman, Stafford L.¹ 

[1] Univ Bristol, Sch Clin Sci, Fac Med & Dent, Henry Wellcome Labs Integrat Neurosci & Endocrino, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England

[2] UCL Sch Pharm, Res Dept Pharmaceut, 29-39 Brunswick Sq, London WC1N 1AX, England

关键词: Glucocorticoid pulsatility;    Ultradian rhythmicity;    Glucocorticoid-based therapeutics;    Neuropsychopathology;    Glucocorticoid neurodynamics;    Mineralocorticoid receptors;    Glucocorticoid receptors;   

DOI  :  10.1016/j.neubiorev.2015.11.009

来源: Elsevier

【 摘 要 】

Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region- and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid- and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradiari pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free