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Stress Research: Past, Present, and Future

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Neuroscience in the 21st Century

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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 hypothalamus-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

5-HT:

5-Hydroxytryptamine = serotonin

5-HTT:

Serotonin transporter

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

LTP:

Long-term potentiation

mdr:

Multidrug resistance

mEPSC:

Miniature excitatory postsynaptic current

MR:

Mineralocorticoid receptor

POMC:

Pro-opiomelanocortin

PPI:

Prepulse inhibition

PVN:

Paraventricular nucleus

SHRP:

Stress hyporesponsive period

SNP:

Single nucleotide polymorphism

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Authors and Affiliations

  1. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

    E. Ronald de Kloet

  2. Department of Neuroscience and Pharmacology, University Medical Center Utrecht Rudolf Magnus Institute of Neuroscience, Utrecht, The Netherlands

    Marian Joëls

  3. University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Marian Joëls

Authors
  1. E. Ronald de Kloet
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  2. Marian Joëls
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Correspondence to E. Ronald de Kloet .

Editor information

Editors and Affiliations

  1. Rockefeller University Lab. Neurobiology & Behaviour, New York, NY, USA

    Donald W. Pfaff

  2. National Institutes of Health (NIH), National Institute of Drug Abuse (NIDA), Rockville, MD, USA

    Nora D. Volkow

  3. Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA

    John Rubenstein

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de Kloet, E.R., Joëls, M. (2021). Stress Research: Past, Present, and Future. In: Pfaff, D.W., Volkow, N.D., Rubenstein, J. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6434-1_72-3

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  • DOI: https://doi.org/10.1007/978-1-4614-6434-1_72-3

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