title: Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics.
abstract: 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 ultradian 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.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol BS1 3NY, United Kingdom. Electronic address: kk13382@bristol.ac.uk.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kalafatakis
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol BS1 3NY, United Kingdom. Electronic address: georgina.russell@bristol.ac.uk.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Russell
authors.affiliation: Research Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom. Electronic address: a.zarros@ucl.ac.uk.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zarros
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol BS1 3NY, United Kingdom. Electronic address: stafford.lightman@bristol.ac.uk.
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D018161:Receptors, Mineralocorticoid
keywords: Glucocorticoid neurodynamics; Glucocorticoid pulsatility; Glucocorticoid receptors; Glucocorticoid-based therapeutics; Mineralocorticoid receptors; Neuropsychopathology; Ultradian rhythmicity