Elsevier

Biological Psychiatry

Volume 67, Issue 11, 1 June 2010, Pages 1106-1109
Biological Psychiatry

Brief Report
Primate Early Life Stress Leads to Long-Term Mild Hippocampal Decreases in Corticosteroid Receptor Expression

https://doi.org/10.1016/j.biopsych.2009.12.016Get rights and content

Background

Expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) genes are moderately reduced in several brain regions in depression. These reductions could be partly due to early life stress (ELS), which predicts emotional disorders. Controlled primate studies are important to test whether ELS sufficient to induce long-term emotional changes also induces long-term altered MR and/or GR brain expression.

Methods

In the common marmoset, ELS of daily 30–120-min social isolation across month-1 resulted in some long-term changes in homeostasis and emotional behavior. In some of these same subjects, the aim of this study was to use marmoset-specific riboprobes to determine whether ELS produced long-term effects on brain MR and GR gene expression.

Results

At adolescence, relative to control subjects, ELS marmosets exhibited mildly reduced messenger RNA signal for both MR (−15%, p = .05) and GR (−13%, p = .02) in hippocampus—primarily CA1-2—but not in prefrontal cortex, other cortical regions, or hypothalamus.

Conclusions

In adolescent marmoset monkey brains, reduced hippocampal expression of MR and GR are consistent chronic-indicators of ELS. It is unlikely that these chronic, mild, specific reductions were acute-mediators of the observed long-term emotional effects of ELS. However, they do suggest involvement of hippocampal MR/GR in the neurodevelopmental effects of ELS.

Section snippets

Methods and Materials

For a complete description of methods and materials see Supplement 1.

Early deprivation (ED) comprised separation of infant from parent and isolation in a neutral environment for 30–120 min/day on postnatal Days 2–28. The control procedure (CON) was handling of the infant on the parent. Otherwise, all subjects remained with the family group and were studied longitudinally in terms of physiology and behavior. Subjects were killed at age 48 weeks. There were 11 ED subjects, 7 male and 4 female,

Results

Relative expression levels of MR mRNA were DG > CA1-4 > Cortex > PFC. In hippocampus (Figures 1A–1E), there was a significant main effect of Manipulation, indicating that MR mRNA levels were significantly reduced in ED relative to CON subjects [F(1,16) = 4.38, p = .05], with no effect of Gender (p > .1; Table S1 in Supplement 1). A-posteriori analysis of individual areas revealed a significant reduction in ED versus CON in CA2 [F(1,16) = 7.59, p = .01] (reduction in mean value = −16%) and CA1 [F

Discussion

This study demonstrates that ELS in primate infants leads in adolescence to mild reductions in MR and GR gene expression in hippocampus and not in PFC, cortex, or paraventricular nucleus. The ED and CON siblings had been studied in vivo, and several depression-relevant physiological and behavioral effects had been demonstrated. In adult human probands of unknown early life history, depression is associated with mild–moderate reductions in hippocampal MR (−20%/−30%) (6) and GR (−20%) (6, 9)

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Authors DA and RD-H contributed equally to this work.

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