Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

Shoener, Jennifer A; Baig, Romana; Page, Kathleen Creed

doi:10.1152/ajpregu.00757.2004

Cited by 101 publications

(77 citation statements)

References 62 publications

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“…A programmed increase in responsiveness of the rat adrenal to stress is in line with previous reports showing enhanced activity of the adult HPA axis at both the hypothalamic and pituitary levels after fetal glucocorticoid excess. Thus, Shoener et al (2006) reported elevated expression of hypothalamic CRH in adult offspring of dexamethasone-treated mothers, and perinatal dexamethasone treatment was shown to increase pituitary corticotroph number in female offspring ( John et al 2006). Our observation that adrenal Mc2r expression is elevated in offspring of dexamethasone-treated mothers suggests that an enhanced HPA reactivity also involves greater responsiveness at the level of the adrenal (i.e.…”

Section: Discussionmentioning

confidence: 63%

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

Waddell¹,

Bollen²,

Wyrwoll³

et al. 2010

Journal of Endocrinology

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Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0 . 75 mg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/ reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.

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Section: Discussionmentioning

confidence: 63%

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

Waddell¹,

Bollen²,

Wyrwoll³

et al. 2010

Journal of Endocrinology

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“…In this model of LBW, we studied the effects of ESC treatment on insulin sensitivity and HPA axis activity in a rat model of LBW (17,64). This model has previously been shown to be insulin resistant and to have HPA axis hyperactivity, pituitary hyperplasia of the ACTH-producing cells, and increased ACTH secretion (17,64).…”

Section: Discussionmentioning

confidence: 99%

Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

Buhl

Jensen

Jessen

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4 -5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser 473 phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P Ͻ 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P Ͻ 0.05 vs. Cx), whole body insulin resistance (P Ͻ 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P Ͻ 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser 473 phosphorylation. The ESC treatment normalized corticosterone secretion (P Ͻ 0.05 vs. LBW), whole body insulin sensitivity (P Ͻ 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P Ͻ 0.05), and red muscle PKB Ser 473 phosphorylation (P Ͻ 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.selective serotonin reuptake inhibitors STRESS MAY BE INVOLVED IN THE DEVELOPMENT of major Western lifestyle disorders such as cardiovascular disease and the metabolic syndrome (53,59,61). Particularly in humans born with low birth weight (LBW) (e.g., birth weight Ͻ2,500 g), stressrelated psychiatric illness and metabolic disturbances seem to coexist, and the prevalence of conditions associated with psychological stress, such as melancholic depression, is increased in subjects born with LBW (35). In addition, these individuals also have a higher prevalence of type 2 diabetes (23, 57, 80) that is potentially due to early development of insulin resistance. Hence, the LBW condition can be considered as both a predepressive and a prediabetic state. However, the exact mechanisms responsible for these changes and whether they are associated are still debated.Recently, impairments in hippocampal structure and function have been proposed to account for some of the phenotypic characteristics of LBW (21,40,63). Hippocampus regulates the overall circadian tonus of the hypothalamic-pituitary-adrenal (HPA) axis, and accordingly, the processes involved in corticosteroid regulation in LBW have been studied extensively. At this point the HPA axis in LBW has been studied at various developmental ...

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“…4). Whereas there is much information about the long-term effects of early-life glucocorticoids on levels of its two receptors in the hippocampus, GR [47,107,148] and mineralocorticoid receptor (MR;148,130), little is known about the effects of these hormones on either hippocampal CRH or the CRH receptor, CRF 1 . In adult rats, administration of the synthetic glucocorticoid hormone, dexamethasone, does not influence CRH levels in the hippocampus [32].…”

Section: Interactions Among Glucocorticoid-and Crh-mediated Mechanismsmentioning

confidence: 99%

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

Fenoglio¹,

Brunson²,

Baram³

2006

Frontiers in Neuroendocrinology

192

138

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Whereas genetic factors contribute crucially to brain function, early-life events, including stress, exert long-lasting influence on neuronal function. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning and memory. Using a novel immaturerodent model, we describe the deleterious consequences of chronic early-life 'psychological' stress on hippocampus-dependent cognitive tasks. We review the cellular mechanisms involved and discuss the roles of stress-mediating molecules, including corticotropin releasing hormone, in the process by which stress impacts the structure and function of hippocampal neurons. KeywordsNeonatal; Rat; Human; Stress; Memory; Hippocampus; Corticotropin releasing hormone; CRF; Hypothalamic pituitary adrenal axis; Neuroplasticity Early-life events interact with genetic factors to influence hippocampal function long-termBrain function and dysfunction throughout life are determined by the interaction of genetic factors with 'acquired' environmental events, signals and stimuli [100]. Events that occur early in life are capable of exerting effects that persist throughout adulthood. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning, memory storage and retrieval, and general cognitive function [105,41,65]. Indeed, early-life events, via complex interactions with genetic factors [106,120], have been suspected to be a major determinant of smaller hippocampal volume and long-term cognitive dysfunction in preterm infants [111,17] and may play a role in certain affective and dementing disorders in the adult and aging human [100,26,120]. This review focuses on the mechanisms by which certain early-life events influence populations of hippocampal neurons acutely, and impact the function and integrity of the hippocampus long-term. Studying early-life stress may be used to probe the molecular mechanisms involved in experience-evoked hippocampal neuroplasticityStress may provide a salient example of early-life experience that might exert long-lasting influence on the brain, because (1) over 50% of the world's children are exposed to stress [139] and (2) evidence from both human and animal studies suggests that early-life stress has profound effects on cognitive function and emotional health.Stress has been shown to influence the hippocampus in a number of important ways. Whereas acute mild stress rapidly enhances synaptic efficacy and learning and memory processes [131,45,91,123], chronic or severe activation of the stress response early in life has been shown to be potentially injurious in both humans [6,120,147] and experimental animals [120,31]. For example, severe childhood psychological stress (neglect and abuse) correlates with a higher incidence of learning disabilities later in life, including those learning and memory functions requiring an intact hippocampus [121,50]. Further, MRI studies have suggested that adults subjected to abuse (a measure of chronic stress) ...

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Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

Cited by 101 publications

References 62 publications

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

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