Gestational hypoxia alone or combined with restraint sensitizes the hypothalamic–pituitary–adrenal axis and induces anxiety-like behavior in adult male rat offspring

Fan, Junming; Chen, X.-Q.; Jin, Haiming; Du, Jianhe

doi:10.1016/j.neuroscience.2009.02.009

Cited by 70 publications

(58 citation statements)

References 63 publications

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“…Considering such interactions with stress-responsive neuroendocrine systems, it is plausible that the amygdala is a primary target of the programming effects of maternal stress. Indeed, several lines of evidence have suggested that either maternal stress or prenatal glucocorticoid (GC) exposure increases amygdala-dependent anxiety-like behaviors in offspring (Cratty et al, 1995;Welberg et al, 2001;Fan et al, 2009). In this regard, we also have reported that maternally stressed mice were more vulnerable to chronic stress-evoked anxiety-like behaviors associated with hyperactivity of the corticotrophinreleasing hormone (CRH) system in the amygdala (Chung et al, 2005).…”

Section: Introductionmentioning

confidence: 91%

Impairment of Fear Memory Consolidation in Maternally Stressed Male Mouse Offspring: Evidence for Nongenomic Glucocorticoid Action on the Amygdala

Lee¹,

Son²,

Chung³

et al. 2011

J. Neurosci.

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The environment in early life elicits profound effects on fetal brain development that can extend into adulthood. However, the longlasting impact of maternal stress on emotional learning remains largely unknown. Here, we focus on amygdala-related learning processes in maternally stressed mice. In these mice, fear memory consolidation and certain related signaling cascades were significantly impaired, though innate fear, fear memory acquisition, and synaptic NMDA receptor expression in the amygdala were unaltered. In accordance with these findings, maintenance of long-term potentiation (LTP) at amygdala synapses, but not its induction, was significantly impaired in the maternally stressed animals. Interestingly, amygdala glucocorticoid receptor expression was reduced in the maternally stressed mice, and administration of glucocorticoids (GCs) immediately after fear conditioning and LTP induction restored memory consolidation and LTP maintenance, respectively, suggesting that a weakening of GC signaling was responsible for the observed impairment. Furthermore, microinfusion of a membrane-impermeable form of GC (BSA-conjugated GC) into the amygdala mimicked the restorative effects of GC, indicating that a nongenomic activity of GC mediates the restorative effect. Together, these findings suggest that prenatal stress induces long-term dysregulation of nongenomic GC action in the amygdala of adult offspring, resulting in the impairment of fear memory consolidation. Since modulation of amygdala activity is known to alter the consolidation of emotionally influenced memories allocated in other brain regions, the nongenomic action of GC on the amygdala shown herein may also participate in the amygdaladependent modulation of memory consolidation.

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Section: Introductionmentioning

confidence: 91%

Impairment of Fear Memory Consolidation in Maternally Stressed Male Mouse Offspring: Evidence for Nongenomic Glucocorticoid Action on the Amygdala

Lee¹,

Son²,

Chung³

et al. 2011

J. Neurosci.

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“…2 Neurodevelopmental models link fetal hypoxia with alterations in hormonal and serotonergic functioning, as well as anxiety-like behaviors. 3,4 Birth trauma, specifically ischemic events, has been correlated with reductions in frontal and temporal gray matter and cerebrospinal fluid volume in those at genetic risk for schizophrenia. 1 In nonfamilial schizophrenia, obstetrical complications may be an environmental factor contributing to its development and are associated with lateral ventricular enlargement.…”

Section: Discussionmentioning

confidence: 99%

“…One study showed that gestational hypoxia has the potential to enhance the activity of the hypothalamic-pituitary-adrenal axis and induce anxiety-like behavior in adult rat offspring. 3 The disordered function of the HPA axis is related to the activation of the CRH-CRHR1-NE neural circuit in these rats by enhanced expression of corticotropin-releasing hormone and its receptor (CRHR1) in the paraventricular nucleus and increased levels of norepinephrine and dopamine in the locus ceruleus. 3 It has, therefore, been concluded that stress during pregnancy might be a risk factor for impaired physiologic stress response and the development of anxiogenic behavior in offspring.…”

Section: Discussionmentioning

confidence: 99%

“…3 The disordered function of the HPA axis is related to the activation of the CRH-CRHR1-NE neural circuit in these rats by enhanced expression of corticotropin-releasing hormone and its receptor (CRHR1) in the paraventricular nucleus and increased levels of norepinephrine and dopamine in the locus ceruleus. 3 It has, therefore, been concluded that stress during pregnancy might be a risk factor for impaired physiologic stress response and the development of anxiogenic behavior in offspring. The colocalization of CRH and its receptors and the CRH-NE stress system in the brain has been suggested as a possible neural basis of this behavioral change.…”

Section: Discussionmentioning

confidence: 99%

“…The colocalization of CRH and its receptors and the CRH-NE stress system in the brain has been suggested as a possible neural basis of this behavioral change. 3 Another study demonstrated that insults caused by fetal asphyxiation at critical periods of brain development led to a decrease in dorsal raphe serotonergic neurons and increased anxiety-related behavior, implying that fetal asphyxia may be associated with the development of affective disorders. 4 By defi ning the type and severity of obstetric complications in patients who later develop psychotic illness, it may be possible to identify dominant injuries that constitute vulnerability markers.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A 21-Year-Old Woman Who Had a Complicated Birth

Fichtel¹,

Modhwadia²

2011

Psychiatric Annals

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Changes Induced by Prenatal Stress in Behavior and Brain Morphology: Can They Be Prevented or Reversed?

Weinstock

2014

Perinatal Programming of Neurodevelopment

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This chapter presents a critical analysis of the behavioral alterations reported in the offspring of women exposed to stress and/or depression during pregnancy and the neurochemical and structural changes underlying them. Among the alterations attributed to prenatal stress in humans and experimental rats of both sexes is impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis, anxiety and exaggerated fear of novelty, and decreased social interaction. Learning and attention deficits are more prevalent in boys and male rats. Fear of novelty and anxiety are associated with enlargement of the amygdala and its corticotropin-releasing factor content, and decreased socialization, with lower oxytocin activity in the amygdala. Learning deficits are associated with a decrease in neurogenesis, dendritic complexity, and spine number in the dorsal hippocampus. Fostering prenatally stressed (PS) pups onto control mothers prevents the dysregulation of the HPA axis and heightened anxiety, indicating a role for postnatal factors in their etiology. By contrast, learning impairment and decreased socialization are not affected by this fostering procedure and are therefore prenatally mediated.In spite of their widespread use in depressed pregnant women, selective serotonin reuptake inhibitor (SSRI) antidepressants do not normalize the behavior of their children. When administered during gestation to stressed rats, SSRIs do not reduce anxiety or learning deficits in their offspring. Moreover, when given to unstressed mothers, SSRIs induce anxiety in the offspring. The detrimental effect of SSRIs may result from inhibition of the serotonin transporter exposing the brain to excess amounts of 5-hydroxytryptamine (5-HT) at a critical time during fetal development.

show abstract

Gestational hypoxia alone or combined with restraint sensitizes the hypothalamic–pituitary–adrenal axis and induces anxiety-like behavior in adult male rat offspring

Cited by 70 publications

References 63 publications

Impairment of Fear Memory Consolidation in Maternally Stressed Male Mouse Offspring: Evidence for Nongenomic Glucocorticoid Action on the Amygdala

Impairment of Fear Memory Consolidation in Maternally Stressed Male Mouse Offspring: Evidence for Nongenomic Glucocorticoid Action on the Amygdala

A 21-Year-Old Woman Who Had a Complicated Birth

Changes Induced by Prenatal Stress in Behavior and Brain Morphology: Can They Be Prevented or Reversed?

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