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The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset.

Pryce CR, Aubert Y, Maier C, Pearce PC, Fuchs E - Psychopharmacology (Berl.) (2010)

Bottom Line: Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset.Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset.The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming.

View Article: PubMed Central - PubMed

Affiliation: Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zürich, Schwerzenbach, Switzerland.

ABSTRACT

Rationale: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates.

Objectives: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset.

Results: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset.

Conclusions: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming.

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Related in: MedlinePlus

Comparison of the effects of saline injection and DEX/CRH neuroendocrine challenge on a plasma ACTH and b plasma cortisol titres, in adolescent ED and CON common marmoset twins (N = 6, 6). Values are mean ± SEM. For ACTH, there was a significant manipulation × sample interaction and a significant main effect of manipulation, with titres increased in ED versus CON subjects. For cortisol, there was a significant manipulation × sample interaction
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Fig8: Comparison of the effects of saline injection and DEX/CRH neuroendocrine challenge on a plasma ACTH and b plasma cortisol titres, in adolescent ED and CON common marmoset twins (N = 6, 6). Values are mean ± SEM. For ACTH, there was a significant manipulation × sample interaction and a significant main effect of manipulation, with titres increased in ED versus CON subjects. For cortisol, there was a significant manipulation × sample interaction

Mentions: In the combined DEX/CRH neuroendocrine challenge, for plasma ACTH titres (Fig. 8a), there was a significant manipulation × sample interaction (F(4, 16) = 4.62, p = 0.01) and a significant main effect of manipulation (F(1, 4) = 14.80, p = 0.02), and a significant main effect of parentage (F(5, 4) = 24.93, p = 0.004); there was a significant main effect of sex (F(1, 4) = 11.04, p = 0.03), with males exhibiting higher ACTH titres than females; there was a significant main effect of sample (F(4, 16) = 73.17, p < 0.001) mainly attributable to elevated ACTH levels at post-CRH 1 h. A posteriori comparisons of ED and CON in terms of ACTH titres at the time points SAL AM and CRH 3 h using paired t tests were not significant. When the delta of each subject’s values at these time points relative to its basal value was used, there was a trend effect to an increased delta in ED versus CON subjects at SAL AM (t(5) = 2.103, p = 0.09) and CRH 3 h (t(5) = −2.410, p = 0.06). For plasma cortisol titres (Fig. 8b), there was a significant interaction of manipulation × sample (F(4, 16) = 3.88, p = 0.02). There was a significant main effect of Sample (F(4, 16) = 19.51, p < 0.001) mainly attributable to low levels of cortisol at the DEX AM and Pre-CRH time points. A posteriori comparison of ED and CON subjects at SAL AM and CRH 3 h did not yield statistical significance and this was also the case using delta values relative to basal titres.Fig. 8


The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: studies in rhesus macaque and common marmoset.

Pryce CR, Aubert Y, Maier C, Pearce PC, Fuchs E - Psychopharmacology (Berl.) (2010)

Comparison of the effects of saline injection and DEX/CRH neuroendocrine challenge on a plasma ACTH and b plasma cortisol titres, in adolescent ED and CON common marmoset twins (N = 6, 6). Values are mean ± SEM. For ACTH, there was a significant manipulation × sample interaction and a significant main effect of manipulation, with titres increased in ED versus CON subjects. For cortisol, there was a significant manipulation × sample interaction
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045510&req=5

Fig8: Comparison of the effects of saline injection and DEX/CRH neuroendocrine challenge on a plasma ACTH and b plasma cortisol titres, in adolescent ED and CON common marmoset twins (N = 6, 6). Values are mean ± SEM. For ACTH, there was a significant manipulation × sample interaction and a significant main effect of manipulation, with titres increased in ED versus CON subjects. For cortisol, there was a significant manipulation × sample interaction
Mentions: In the combined DEX/CRH neuroendocrine challenge, for plasma ACTH titres (Fig. 8a), there was a significant manipulation × sample interaction (F(4, 16) = 4.62, p = 0.01) and a significant main effect of manipulation (F(1, 4) = 14.80, p = 0.02), and a significant main effect of parentage (F(5, 4) = 24.93, p = 0.004); there was a significant main effect of sex (F(1, 4) = 11.04, p = 0.03), with males exhibiting higher ACTH titres than females; there was a significant main effect of sample (F(4, 16) = 73.17, p < 0.001) mainly attributable to elevated ACTH levels at post-CRH 1 h. A posteriori comparisons of ED and CON in terms of ACTH titres at the time points SAL AM and CRH 3 h using paired t tests were not significant. When the delta of each subject’s values at these time points relative to its basal value was used, there was a trend effect to an increased delta in ED versus CON subjects at SAL AM (t(5) = 2.103, p = 0.09) and CRH 3 h (t(5) = −2.410, p = 0.06). For plasma cortisol titres (Fig. 8b), there was a significant interaction of manipulation × sample (F(4, 16) = 3.88, p = 0.02). There was a significant main effect of Sample (F(4, 16) = 19.51, p < 0.001) mainly attributable to low levels of cortisol at the DEX AM and Pre-CRH time points. A posteriori comparison of ED and CON subjects at SAL AM and CRH 3 h did not yield statistical significance and this was also the case using delta values relative to basal titres.Fig. 8

Bottom Line: Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset.Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset.The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming.

View Article: PubMed Central - PubMed

Affiliation: Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zürich, Schwerzenbach, Switzerland.

ABSTRACT

Rationale: Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates.

Objectives: Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset.

Results: Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset.

Conclusions: Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming.

Show MeSH
Related in: MedlinePlus