Repeated maternal glucocorticoid treatment affects activity and hippocampal NMDA receptor expression in juvenile guinea pigs

Owen, Dawn; Matthews, Stephen G.

doi:10.1113/jphysiol.2006.122887

Cited by 46 publications

(29 citation statements)

References 46 publications

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“…For this reason, 1 mg/kg betamethasone (as compared with an average dose of 0.2 mg/kg used clinically in human pregnancies) was administered to pregnant dams subcutaneously at 48 and 24 h before delivery to stimulate fetal lung maturation. This dosage has been shown to exert effects on the guinea pig similar to those seen clinically in humans (35,36). Term cesarean sections were performed at 69 d gestation or earlier if the pubic symphysis had been open for 2 consecutive days.…”

Section: Cesarean Section Deliverymentioning

confidence: 99%

The guinea pig as an animal model for studying perinatal changes in microvascular function

et al. 2011

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INTRODUCTION: Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function. RESULTS: Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals. DISCUSSION: These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior. METHODS: Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age. In term infants, the circulation undergoes rapid and extensive changes in the initial hours of extrauterine life to allow the infant to effectively deal with extrauterine systemic vascular resistance and hence provide normal and adequate perfusion of tissues (1-3). The transitional circulation of preterm neonates (especially those born at ≤30 wk gestation) differs significantly from infants born at full term. In the preterm infant, several crucial physiologic responses to extrauterine life are commonly delayed, allowing for persistence of atrial and ductal shunting and inappropriate blood flow throughout the periphery during the perinatal period (4)(5)(6)(7)(8).Previous studies in preterm infants suggest that abnormal microvascular tone, characterized by inappropriate vasodilatation of the peripheral microvasculature, may contribute to the development of circulatory compromise (4,8). These studies found that the functional integrity of the microvasculature (including appropriate control of vasodilatation) in preterm neonates is significantly altered as compared with neonates born at later gestational ages (GAs). Very preterm neonates (born at 24-28 wk GA) are known to have significantly higher microvascular blood flow at 24 h postnatal age than preterm neonates born at 29-34 wk GA and neonates born at term. High baseline microvascular blood flow in premature infants is significantly correlated with clinical illness severity and poor outcome in the immediate postnatal period (4,9). Such dysfunction in the microvasculature is also a well-established observation associated with the onset of other causes of multisystem organ failure in neonates (10).In addition to disorders relating to short gestation, intrauterine growt...

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Section: Cesarean Section Deliverymentioning

confidence: 99%

The guinea pig as an animal model for studying perinatal changes in microvascular function

et al. 2011

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“…In guinea pigs, repeated prenatal sGC treatment produces sex-specific effects with females exhibiting hyperactivity in an open-field test and a concomitant decrease in expression of the hippocampal N -Methyl- D -Aspartate receptor subunit 70 as well as altered HPA regulation 71. Likewise, young and adult rats born to dams treated with dexamethasone display sex-specific changes in locomotor and habituation activity in an anxiety related behavioral test 72 and prenatally stressed rats display significantly more depressive and anxious behaviors 73–75.…”

Section: Commentmentioning

confidence: 99%

Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

Rodriguez¹,

Zürcher²,

Keenan³

et al. 2011

American Journal of Obstetrics and Gynecology

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Objective-We investigated effects of three weekly courses of fetal betamethasone (βM) exposure on motivation and cognition in juvenile baboon offspring utilizing the Cambridge Neuropsychological Test Automated Battery.Study design-Pregnant baboons (Papio sp.) received two injections of saline control (C) or 175 μg/kg βM 24h apart at 0.6, 0.65 and 0.7 gestation. Offspring [Female (FC), n = 7 and Male (MC), n = 6; Female (FβM), n = 7 and Male (MβM), n = 5] were studied at 2.6-3.2 years with a progressive ratio test for motivation, simple discriminations (SD) and reversals (SR) for associative learning and rule change plasticity, and an intra-dimensional/extra-dimensional (IDED) set-shifting test for attention allocation. Conclusion-This central nervous system developmental programming adds growing concerns of long-term effects of repeated fetal synthetic glucocorticoid exposure. In summary, behavioral effects observed show sex specific differences in resilience to multiple fetal βM exposures. Results-βM

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“…A direct relationship between brain corticosteroid receptor levels and anxiety-like behaviour is supported by the phenotype of transgenic mice with disrupted GR expression in the brain, which have markedly reduced anxiety behaviours [120]. NMDARs (N-methyl-d-aspartate receptors) have also been implicated in the programming of behaviour; in guinea pigs, exposure to repeated doses of betamethasone prenatally is associated with altered expression of the hippocampal NMDAR subunits and increased locomotor activity in females [121].…”

Section: Programming Offspring Behaviourmentioning

confidence: 99%

Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease

2007

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Compelling epidemiological evidence suggests that exposure to an adverse intrauterine environment, manifested by low-birth weight, is associated with cardiometabolic and behavioural disorders in adulthood. These observations have led to the concept of 'fetal programming'. The molecular mechanisms that underlie this relationship remain unclear, but are being extensively investigated using a number of experimental models. One major hypothesis for early life physiological programming implicates fetal overexposure to stress (glucocorticoid) hormones. Several animal studies have shown that prenatal glucocorticoid excess, either from endogenous overproduction with maternal stress or through exogenous administration to the mother or fetus, reduces birth weight and causes lifelong hypertension, hyperglycaemia and behavioural abnormality in the offspring. Intriguingly, these effects are transmitted across generations without further exposure to glucocorticoids, which suggests an epigenetic mechanism. These animal observations could have huge implications if extrapolated to humans, where glucocorticoids have extensive therapeutic use in obstetric and neonatal practice.

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Repeated maternal glucocorticoid treatment affects activity and hippocampal NMDA receptor expression in juvenile guinea pigs

Cited by 46 publications

References 46 publications

The guinea pig as an animal model for studying perinatal changes in microvascular function

The guinea pig as an animal model for studying perinatal changes in microvascular function

Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons

Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease

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