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.
Key Words
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References
- Toward a comprehensive development model for major depression in women.Am J Psychiatry. 2002; 159: 1133-1145
- A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up.Arch Gen Psychiatry. 2007; 64: 49-56
- Child maltreatment and the developing HPA axis.Horm Behav. 2006; 50: 632-639
- Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation.Biol Psychiatry. 2004; 55: 367-375
- Epigenetic regulation of the glucocorticoid receptor in human brain associates with child abuse.Nat Neurosci. 2009; 12: 342-348
- Regulation of serotonin1A, glucocorticoid, annd mineralocorticoid receptor in rat and human hippocampus: Implications for the neurobiology of depression.Biol Psychiatry. 1998; 43: 547-573
- Decreased expression of mineralocorticoid receptor mRNA in the prefrontal cortex in schizophrenia and bipolar disorder.Int J Neuropsychopharmacol. 2004; 7: 143-153
- Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: The presence of multiple receptor imbalances.Mol Psychiatry. 2008; 13: 786-799
- Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders.Mol Psychiatry. 2002; 7: 985-994
- Hypothalamic-pituitary-adrenocortical system dysregulation and new treatment strategies in depression.Expert Rev Neurother. 2009; 9: 1005-1019
- Repeated parental deprivation in the infant common marmoset (Callithrix jacchus, Primates) and analysis of its effects on early development.Biol Psychiatry. 2002; 52: 1037-1046
- Evidence for altered monoamine activity and emotional and cognitive disturbance in marmoset monkeys exposed to early life stress.Ann N Y Acad Sci. 2004; 1032: 245-249
- Deprivation of parenting disrupts development of homeostatic and reward systems in marmoset monkey offspring.Biol Psychiatry. 2004; 56: 72-79
- Postnatal ontogeny of hippocampal expression of the mineralocorticoid and glucocorticoid receptors in the common marmoset.Eur J Neurosci. 2005; 21: 1521-1535
- Calcyon mRNA expression in the frontal-striatal circuitry and its relationship to vesicular processes and ADHD.Behav Brain Funct. 2007; 3: 33
- How do you feel—now?.Nat Rev Neurosci. 2009; 10: 59-70
- Behavioral and physiological effects of an infant-neglect manipulation in a bi-parental, twinning primate: Impact is dependent on familial factors.Psychoneuroendocrinology. 2007; 32: 331-349
- Post-traumatic stress disorder in children and adolescents: From Sigmund Freud's “trauma” to psychopathology and the (dys)metabolic syndrome.Horm Metab Res. 2007; 39: 413-419
- Brain corticosteroid receptor balance in health and disease.Endocr Rev. 1998; 19: 269-301
- Early parental deprivation in the marmoset monkey produces long-term changes in hippocampal expression of genes involved in synaptic plasticity and implicated in mood disorder.Neuropsychopharmacology. 2009; 34: 1381-1394
Article info
Publication history
Published online: February 05, 2010
Accepted:
December 14,
2009
Received in revised form:
October 16,
2009
Received:
August 3,
2009
Footnotes
Authors DA and RD-H contributed equally to this work.
Identification
Copyright
© 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.