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Review
. 2010 Nov;52(7):661-70.
doi: 10.1002/dev.20490.

Plasticity of the stress response early in life: mechanisms and significance

Aniko Korosi  1 , Tallie Z Baram
Affiliations
Review

Plasticity of the stress response early in life: mechanisms and significance

Aniko Korosi et al. Dev Psychobiol. 2010 Nov.

Abstract

The concept that early-life experience influences the brain long-term has been extensively studied over the past 50 years, whereas genetic factors determine the sequence and levels of expression of specific neuronal genes, this genetic program can be modified enduringly as a result of experience taking place during critical developmental periods. This programming is of major importance because it appears to govern many behavioral and physiological phenotypes and promote susceptibility or resilience to disease. An established example of the consequences of early-life experience-induced programming includes the effects of maternal care, where patterns of augmented care result in decreased neuroendocrine stress responses, improved cognition and resilience to depression in the recipients of this care. Here, we discuss the nature and mechanisms of this programming phenomenon, focusing on work from our lab that was inspired by Seymour Levine and his fundamental contributions to the field.

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Figures

FIGURE 1
FIGURE 1
The spectrum and sequence of molecular and hormonal changes induced by maternal care alterations via early-life handling. Corticotropin releasing hormone (CRH) expression in the hypothalamic paraventricular nucleus (PVN) of adult rats handled on postnatal (P) days P2–P9 is reduced, as are plasma ACTH and corticosterone (CORT) responses to stressors. Glucocorticoid receptor (GR) expression in the hippocampus is increased in these rats compared with controls. These changes occur in a sequential manner with reduced CRH present already by P9, followed by reduced ACTH response to stress by P23 and reduced hippocampal GR appearing between P23 and P45. The sequence of changes supports the concept of CRH modulation as an early and essential step in bridging handling-induced enhanced maternal care and the enduring changes in the HPA system.
FIGURE 2
FIGURE 2
Augmented early-life experience leads to early-onset and persistent reduction of CRH expression in parvocellular PVN at both mRNA and protein levels. (A) Representative bright-field photomicrographs of coronal sections at the level of the PVN from undisturbed controls and handled rats. The sections were subject to in situ hybridization for CRH mRNA. (B) Quantitative analysis of CRH mRNA expression in the two groups: CRH mRNA expression was reduced by 52% in postnatal day (P) 9, handled rats compared with undisturbed controls. (C) Bright-field photomicrographs, taken under similar viewing parameters, showing CRH immunohistochemistry in PVN of control and handled rats. (D) Quantitative analysis of the numbers of CRH immunoreactive (ir) neurons and (E) intensity of the immunoreactivity. The changes observed for mRNA expression were translated to protein levels as apparent from the ~20% reduction in the intensity of CRH expression in handled rats. (F,G) Representative autoradiographs after CRH mRNA in situ hybridization, and quantification of CRH mRNA signal in adult control and handled rat PVN. CRH expression in handled adult rats was 50% lower compared to controls, indicating that repressed CRH expression, found on P9, was long-lasting. (H,I,J) Bright-field photomicrographs and quantitative analysis of CRH immunohistochemistry in adult PVN. The enduring suppression of CRH expression observed at the mRNA level was translated to the protein level as evident from the ~21% reduction of CRH-ir cells in the handled rats. 3rd = third ventricle. Scale bars in A,F: 500 μm, in C,H: 200 μm. *p <.05. (Figure modified from Korosi et al., 2010.)
FIGURE 3
FIGURE 3
Sensory stimulation of pups by the dam is enhanced daily after brief separation of pups from their mother. (A) Maternal stimulation of the pups, and specifically licking was observed and quantified daily from P2 to P8 during the 30 min following the return of separated pups and dams to home cages (handling procedure starting at 08:30 AM; light on at 07:00 AM.). Duration of the sensory stimulation of the pups was significantly higher in litters that were briefly separated (handled) compared to control litters on each day (n = 16 dams per group; repeated measure ANOVA F1,31 = 39.94, p < .0001). (B) Collapsed for the whole week, duration of nurturing activity of the dams was twofold higher in handled litters compared with controls. *p <.0001.
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