Stress Research: Past, Present, and Future

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.

Abbreviation

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

Notes

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.

Further Reading

  1. Bartsch T (2012) The clinical neurobiology of the hippocampus. Oxford University Press; in pressGoogle Scholar
  2. Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes? Mol Psychiatr 14:746–754CrossRefGoogle Scholar
  3. Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joëls M, Krugers H. (2008) Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28:6037–6045PubMedCrossRefGoogle Scholar
  4. Champagne DL, de Kloet ER, Joëls M (2009) Fundamental aspects of the impact of glucocorticoids on the (immature) brain. Semin Fetal Neonatal Med 14:136–142PubMedCrossRefGoogle Scholar
  5. Datson NA, van der Perk J, de Kloet ER, Vreugdenhil E (2001) Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression. Eur J Neurosci 14:675–689PubMedCrossRefGoogle Scholar
  6. Datson NA, Speksnijder N, Mayer JL (2011) The transcriptional response to chronic stress and glucocorticoid receptor blockade in the hippocampal dentate gyrus. Hippocampus, 22:359–371Google Scholar
  7. Derijk RH, van Leeuwen N, Klok MD, Zitman FG (2008) Corticosteroid receptor-gene variants: modulators of the stress-response and implications for mental health. Eur J Pharmacol 585:492–501PubMedCrossRefGoogle Scholar
  8. de Kloet ER, Oitzl MS, Joëls M (1999) Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci 22:422–426PubMedCrossRefGoogle Scholar
  9. de Kloet ER, Joëls M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475PubMedCrossRefGoogle Scholar
  10. Holsboer F, Ising M (2010) Stress hormone regulation: biological role and translation into therapy. Ann Rev Psychol 61(81–109):C1–C11Google Scholar
  11. Joëls M (2006) Corticosteroid effects in the brain: U-shape it. Trends Pharmacol Sci 27:244–250PubMedCrossRefGoogle Scholar
  12. Joëls M, Baram TZ (2009) The neuro-symphony of stress. Nat Rev Neurosci 10:459–466PubMedGoogle Scholar
  13. Joëls M, Pu Z, Wiegert O, Oitzl MS, Krugers HJ (2006) Learning under stress: how does it work? Trends Cogn Sci 10:152–158PubMedCrossRefGoogle Scholar
  14. Joëls M, Karst H, deRijk R, de Kloet ER (2008) The coming out of the brain mineralocorticoid receptor. Trends Neurosci 31:1–7PubMedCrossRefGoogle Scholar
  15. Karst H, Berger S, Turiault M, Tronche F, Schütz G, Joëls M (2010a) Mineralocorticoid receptors are indispensible for nongenomic modulation of hippocampal glutamate transmission by cortiocsterone. Proc Natl Acad Sci USA 102:19204–19207CrossRefGoogle Scholar
  16. Karst H, Berger S, Erdmann G, Schütz G, Joëls M (2010b) Metaplasticity of amygdalar responses to the stress hormone corticosterone. Proc Natl Acad Sci USA 107:14449–14454PubMedCrossRefGoogle Scholar
  17. Klok MD, Giltay EJ, Van der Does AJW, Geleijnse JM, Antypa N, Penninx BWJH, de Geus EJC, Willemsen G, Boomsma DI, Van Leeuwen N, Zitman FG, de Kloet ER, de Rijk RH (2011) A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females. Trans Psychiatr 1:e62CrossRefGoogle Scholar
  18. Krugers HJ, Hoogenraad CC, Groc L (2010) Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory. Nat Rev Neurosci 11:675–681PubMedCrossRefGoogle Scholar
  19. Levine S (2005) Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology 30:939–994PubMedCrossRefGoogle Scholar
  20. Lightman SL, Conway-Campbell BL (2010) The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration. Nat Rev Neurosci 11:710–718PubMedCrossRefGoogle Scholar
  21. Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445PubMedCrossRefGoogle Scholar
  22. McEwen BS, Wingfield JC (2010) What is in a name? Integrating homeostasis, allostasis and stress. Horm Behav 57:105–111PubMedCrossRefGoogle Scholar
  23. Oakley RH, Cidlowski JA (2011) Cellular processing of the glucocorticoid receptor gene and protein: new mechanisms for generating tissue-specific actions of glucocorticoids. J Biol Chem 286:3177–3184PubMedCrossRefGoogle Scholar
  24. Oitzl MS, de Kloet ER (1992) Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav Neurosci 106:62–71PubMedCrossRefGoogle Scholar
  25. Oitzl MS, Champagne DL, van der Veen R, de Kloet ER (2010) Brain development under stress: hypotheses of glucocorticoid actions revisited. Neurosci Biobehav Rev 34:853–866PubMedCrossRefGoogle Scholar
  26. Oitzl MS, Schwabe L, Aggleton JP (2012) Memory formation: its changing face. Neurosci Biobehav Rev Mar 19. [Epub ahead of print]Google Scholar
  27. Roozendaal B, McEwen BS, Chattarji S (2009) Stress, memory and the amygdala. Nat Rev Neurosci 10:423–433PubMedCrossRefGoogle Scholar
  28. Sarabdjitsingh RA, Isenia S, Polman A, Mijalkovic J, Lachize S, Datson N, de Kloet ER, Meijer OC (2010) Disrupted corticosterone pulsatile patterns attenuate responsiveness to glucocorticoid signaling in rat brain. Endocrinology 151:1177–1186PubMedCrossRefGoogle Scholar
  29. Sibug RM, de Koning J, Tijssen AM, de Ruiter MC, de Kloet ER, Helmerhorst FM (2005) Urinary gonadotrophins but not recombinant gonadotrophins reduce expression of VEGF120 and its receptors flt-1 and flk-1 in the mouse uterus during the peri-implantation period. Hum Reprod 20:649–656PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  1. 1.Medical PharmacologyLACDR/LUMC, Leiden UniversityLeidenThe Netherlands
  2. 2.Department of Neuroscience and PharmacologyUniversity Medical Center Utrecht Rudolf Magnus Institute of NeuroscienceUtrechtThe Netherlands

Personalised recommendations