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Stress Research: Past, Present, and Future

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Neuroscience in the 21st Century

Abstract

This chapter starts with highlighting the evolution of the stress concept and the discovery of mediators that coordinate stress adaptation. Next, progress in the unraveling of the mechanism underlying the action of these stress mediators is discussed, focusing on glucocorticoids as the end product of the hypothalamic pituitary adrenal (HPA) axis. This action exerted by the glucocorticoids is mediated by a dual receptor system: mineralocorticoid (MR) and glucocorticoid receptors (GR). With these receptors as leading theme we present five highlights that illustrate the serendipitous nature of stress research. These five highlights are integrated in the final section which culminates in reflections on the role of stress in mental health. In these reflections we merge the mind-boggling complexity of molecular signaling pathways with neuroendocrine communication integrating body and brain functions. The new insights will be used during the next decennium to target, in an individual-specific fashion, the stress system with the objective to enhance the quality of life.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

ADX:

Adrenalectomy

APO-SUS:

Apomorphine-susceptible

B:

Corticosterone

BLA:

Basolateral amygdala

CRH:

Corticotropin releasing hormone

Dex:

Dexamethasone

ERK:

Extracellular regulated kinase 1/2

F:

Cortisol

GR:

Glucocorticoid receptor

HPA axis:

Hypothalamic-Pituitary-Adrenal axis

5-HT:

5-Hydroxytryptamine = serotonine

5-HTT:

Serotonin transporter

LTP:

Long-term potentiation

MR:

Mineralocorticoid receptor

mdr:

Multidrug resistance

mEPSC:

Miniature excitatory postsynaptic current

POMC:

Pro-opiomelanocortin

PPI:

Prepulse inhibition

PVN:

Paraventricular nucleus

SHRP:

Stress hyporesponsive period

SNP:

Single nucleotide polymorphism

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Acknowledgments

The support by the Royal Netherlands Academy of Arts and Sciences (KNAW), Top Institute-Pharma (TI-Pharma), the Netherlands Scientific Organization (NWO), Human Frontiers in Science program (HFSP) and EU-Eurostress/Eurocores & EU-Lifespan is gratefully acknowledged.

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Authors and Affiliations

  1. Medical Pharmacology, LACDR/LUMC, Leiden University, PO Box 9502 (Einsteinweg 55), Leiden, RA, 2300, The Netherlands

    Dr. E. R. (Ron) de Kloet PhD

  2. Department of Neuroscience and Pharmacology, University Medical Center Utrecht Rudolf Magnus Institute of Neuroscience, P.O. Box 85060, Utrecht, 3508 AB, The Netherlands

    Dr. Marian Joëls

Authors
  1. Dr. E. R. (Ron) de Kloet PhD
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  2. Dr. Marian Joëls
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Corresponding author

Correspondence to E. R. (Ron) de Kloet PhD .

Editor information

Editors and Affiliations

  1. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA

    Donald W. Pfaff

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(Ron) de Kloet, E.R., Joëls, M. (2013). Stress Research: Past, Present, and Future. In: Pfaff, D.W. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1997-6_72

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