Early life trauma decreases glucocorticoid receptors in rat dentate gyrus upon adult re-stress: Reversal by escitalopram

Uys, Joachim D.; Muller, Christo J. F.; Marais, Lelanie; Harvey, Brian H.; Stein, Dan J.; Daniels, Willie M. U.

doi:10.1016/j.neuroscience.2005.08.089

Cited by 57 publications

(36 citation statements)

References 35 publications

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“…The increase in phospho-JNK, such as observed after trauma, once again reflect cellular stress. This is particularly plausible since we have previously shown a decrease in glucocorticoid receptors in traumatized animals [10], possibly stemming from increased inhibition of its transcription by the elevated JNK levels [29]. In addition we also found a decrease in MAP kinase kinase (MEK 1).…”

Section: Discussionsupporting

confidence: 57%

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Large Scale Hippocampal Cellular Distress may Explain the Behavioral Consequences of Repetitive Traumatic Experiences-A Proteomic Approach

et al. 2008

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Early life traumatic experiences are associated with psychopathology in adulthood. This may be due in part to the effects of trauma on hippocampal development and protein expression. The purpose of the study was to investigate the effects of early life trauma and adult re-stress on ventral hippocampal protein expression. Adolescent rats (n = 19) were subjected to a triple stressor on post-natal day 28 followed 7 days later by the first re-stress session and 25 days later (post-natal day 60 = adulthood) by the second re-stress session. Ventral hippocampi were collected on post-natal day 68 for protein expression determinations using protein arrays and 2D-gel electrophoresis with liquid chromatography tandem mass spectrometry. Compared to controls, traumatized animals showed an increase in Ca(2+) homeostatic proteins, dysregulated signaling pathways and energy metabolism enzymes, cytoskeletal protein changes, a decrease in neuroplasticity regulators, energy metabolism enzymes and an increase in apoptotic initiator proteins. These results indicate the extensive impact of trauma on adult brain development and behavior.

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Section: Discussionsupporting

confidence: 57%

“…These animals had high basal corticosterone levels and decreased glucocorticoid receptors in the dentate gyrus of the hippocampus [10]. In addition, traumatized animals also showed a decrease in BDNF in the dorsal hippocampus and a decrease in NT-3 in the dorsal and ventral hippocampus.…”

Section: Introductionmentioning

confidence: 93%

Large Scale Hippocampal Cellular Distress may Explain the Behavioral Consequences of Repetitive Traumatic Experiences-A Proteomic Approach

et al. 2008

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“…Importantly, expression of GR and MR in the hippocampus reaches adult levels by PD21 (for review see McCormick et al (in press). However, exposure to chronic stress during adolescence leads to a decrease in expression of GR and MR in the adult hippocampus (Uys et al, 2006;Schmidt et al, 2007;Sterlemann et al, 2008), possibly reflecting a long-term impairment of the negative feedback system of the HPA. Thus, the sex-dependent effects of chronic adolescent stress on adult neurogenesis might be mediated through changes in GR and MR expression levels or through stressinduced long-term changes in HPA axis function.…”

Section: Exposure To Chronic Stress During Adolescence Alters Hippocamentioning

confidence: 99%

Chronic restraint stress in adolescence differentially influences hypothalamic‐pituitary‐adrenal axis function and adult hippocampal neurogenesis in male and female rats

et al. 2011

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Previous studies have shown a relationship between adversity in adolescence and health outcomes in adulthood in a sex-specific manner. Adolescence is characterized by major changes in stress-responsive regions of the brain, including the hippocampus, the site of ongoing neurogenesis throughout the lifespan. Prepubertal male and female rats exhibit different acute reactions to chronic stress compared to adults, but less is known about whether these stress-induced changes persist into adulthood. Therefore, in this study, we investigated the effects of chronic, intermittent stress during adolescence on basal corticosterone levels, dentate gyrus (DG) volume, and neurogenesis in the hippocampus of adult male and female Sprague-Dawley rats. Adolescent male and female rats were either restrained for 1 h every other day for 3 weeks from postnatal days (PDs) 30-52 at unpredictable times or left undisturbed. All rats received a single injection of bromodeoxyuridine (BrdU; 200 mg/kg) in adulthood on PD70 and were perfused 3 weeks later. Brains were processed for Ki67 (endogenous marker of cell proliferation) and BrdU (to estimate effects on cell survival). In addition, blood samples were taken during the restraint stress period and in adulthood. Results show that males and females exhibit different corticosterone responses to chronic stress during adolescence and that only adult female rats exposed to stress during adolescence show higher basal corticosterone levels compared to nonstressed controls. Furthermore, stressed females showed a reduced number of proliferating and surviving cells in the DG in adulthood compared to nonstressed same-sex controls. The majority of BrdU-labeled cells were co-labeled with NeuN, an endogenous marker of mature neurons, indicating that neurogenesis was decreased in the DG of adult female rats that had undergone chronic restraint stress in adolescence. Although male rats were more responsive to the chronic stress as adolescents showing higher corticosterone levels and reduced body weight, as adults they showed a slight increase in cell survival and no effect of adolescent stress on basal corticosterone levels. These results suggest that stress during adolescence can have effects on hypothalamic-pituitary-adrenal axis function and hippocampus plasticity in adulthood, particularly in female rats.

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“…Efficacy of monoaminergic neurotransmission can also be modulated by MR and GR [84] . With respect to this, it was shown that treatment with antidepressant drugs can enhance hippocampal MR and/or GR expression [85,86] , and reverse a stress-induced decrease in hippocampal GR [87] .…”

Section: Susceptibility To Extinction-induced Despair Accompanied By mentioning

confidence: 99%

Differential Susceptibility to Extinction-Induced Despair and Age-Dependent Alterations in the Hypothalamic-Pituitary-Adrenal Axis and Neurochemical Parameters

et al. 2008

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Clinical studies point to structural differences in the neurobiological mechanisms underlying early versus late onset of depression. However, studies examining the neuropathology of depressive-like behavior induced in the aged rodent are sparse. Extinction of learned behavior induces be- havioral ‘despair’, and is held to provide a conceptual and empirical model of human depression resulting from the withdrawal of reinforcement. We tested whether the neuroendocrinological and chemical concomitants of susceptibility to extinction-induced despair in aged animals differed from adult ones. Following the withholding of reinforcement (extinction of escape from a water maze), a number of aged and adult rats are prone to develop depressive-like behavior, i.e. immobility. Analysis of hypothalamus-pituitary-adrenal (HPA) axis markers revealed an increase in the mineralocorticoid/glucocorticoid receptor (MR/GR) mRNA ratio in the CA1 region of the hippocampus in aged and adult despair animals; however, in dependence on age, divergent changes contributed to the enhanced ratio. While aged despair rats had less GR mRNA, adult despair rats had more MR mRNA. Furthermore, age- and despair-related interactions with hippocampal and cortical steroid receptor co-activators and neurotransmitter contents in diverse brain areas were found. For instance, adult despair rats had an increased, and aged despair rats a decreased, DOPAC/dopamine turnover compared to the respective non-despair group. These results show that neurobiological underpinnings of depression in the aged differ from those of adults, and underline the importance of investigating age-related alterations in HPA axis dynamics in conjunction with neurotransmitter systems to advance our knowledge about neuronal mechanisms of late-life and/or late-onset depression.

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Early life trauma decreases glucocorticoid receptors in rat dentate gyrus upon adult re-stress: Reversal by escitalopram

Cited by 57 publications

References 35 publications

Large Scale Hippocampal Cellular Distress may Explain the Behavioral Consequences of Repetitive Traumatic Experiences-A Proteomic Approach

Large Scale Hippocampal Cellular Distress may Explain the Behavioral Consequences of Repetitive Traumatic Experiences-A Proteomic Approach

Chronic restraint stress in adolescence differentially influences hypothalamic‐pituitary‐adrenal axis function and adult hippocampal neurogenesis in male and female rats

Differential Susceptibility to Extinction-Induced Despair and Age-Dependent Alterations in the Hypothalamic-Pituitary-Adrenal Axis and Neurochemical Parameters

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