Programming of stress pathways: A transgenerational perspective

Constantinof, Andrea; Moisiadis, Vasilis G.; Matthews, Stephen G.

doi:10.1016/j.jsbmb.2015.10.008

Cited by 67 publications

(58 citation statements)

References 62 publications

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“…This has been shown for humans (Chamorro-Garcia and Blumberg, 2014; Veenendaal et al, 2013) and animals (Constantinof et al, 2015; Iqbal et al, 2012). Whether maternal alcohol consumption is specific in its effect on the next generation cannot be ascertained at this date.…”

Section: Discussionsupporting

confidence: 54%

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats

Tunc-Ozcan

Harper

Graf

et al. 2016

Hormones and Behavior

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The neurodevelopmental fetal alcohol spectrum disorder (FASD) is characterized by cognitive and behavioral deficits in the offspring. Conferring the deficits to the next generation would increase overall FASD disease burden and prevention of this transmission could be highly significant. Prior studies showed the reversal of these behavioral deficits by low dose thyroxine (T4) supplementation to the ethanol-consuming mothers. Here we aim to identify whether prenatal ethanol (PE) exposure impairs hippocampus-dependent learning and memory in the second-generation (F2) progeny, and whether T4 administration to the ethanol-consuming dam can prevent it. Sprague-Dawley (S) dams received control diets (ad libitum and nutritional control) or ethanol containing liquid diet with and without simultaneous T4 (0.3mg/l diet) administration. Their offspring (SS F1) were mated with naïve Brown Norway (B) males and females generating the SB F2 and BS F2 progeny. Hippocampus-dependent contextual fear memory and hippocampal expression of the thyroid hormone-regulated type 3 deiodinase, (Dio3) and neurogranin (Nrgn) were assessed. SS F1 PE-exposed females and their SB F2 progeny exhibited fear memory deficits. T4 administration to the mothers of F1 females reversed these deficits. Although SS F1 PE-exposed males also experienced fear memory deficit, this was neither transmitted to their BS F2 offspring nor reversed by prenatal T4 treatment. Hippocampal Dio3 and Nrgn expression showed similar pattern of changes. Grandmaternal ethanol consumption during pregnancy affects fear memory of the matrilineal second-generation progeny. Low dose T4 supplementation prevents this process likely via altering allele-specific and total expression of Dio3 in the hippocampus.

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Section: Discussionsupporting

confidence: 54%

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats

Tunc-Ozcan

Harper

Graf

et al. 2016

Hormones and Behavior

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“…Effects of prolonged DEX treatment may appear only at later developmental stages or in adulthood, and only be noticeable upon challenges to the organism. This is seen in humans or other mammals exposed to high DEX levels during development, which later in life show increased disease susceptibility and altered responses to stress [25,26]. The DEX-treatment related changes to metabolites or gene expression patterns revealed within our data set may provide interesting starting points for understanding the mechanistic principles of such long-term effects.…”

Section: Discussionmentioning

confidence: 89%

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

Weger

Görling

et al. 2016

PLoS Genet

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Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism.

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“…In a broad range of preclinical and clinical studies, prenatal exposure to stress-related conditions has been shown to potently stimulate biological stress pathways,(Constantinof et al, 2015) alter synaptogenesis (Bale et al, 2010, Singh-Taylor et al, 2015) and result in changes in structural brain development (Qiu et al, 2015, Qiu et al, 2013, Rifkin-Graboi et al, 2013, Rifkin-Graboi et al, 2015, Van Dam et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Prenatal stress alters amygdala functional connectivity in preterm neonates

Mayes

Kwon

Lacadie

et al. 2016

NeuroImage: Clinical

111

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Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders.We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used.When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth.Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

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Programming of stress pathways: A transgenerational perspective

Cited by 67 publications

References 62 publications

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats

Thyroxine administration prevents matrilineal intergenerational consequences of in utero ethanol exposure in rats

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

Prenatal stress alters amygdala functional connectivity in preterm neonates

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