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

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Perinatal Programming of Neurodevelopment

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 10))

Abstract

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 changles 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.

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Abbreviations

ADHD:

Attention deficit hyperactivity disorder

BrdU:

5-bromo-2ʹ-deoxyuridine

CeA:

Central nucleus of the amygdala

COR:

Corticosterone

CRF:

Corticotropin-releasing factor

CRF-BP:

Corticotropin-releasing factor binding protein

CRFR1:

Corticotropin-releasing factor receptor 1

CRFR2:

Corticotropin-releasing factor receptor 2

DG:

Dentate gyrus

DCX:

Doublecortin

EE:

Environmental enrichment

EPM:

Elevated plus maze

HPA:

Hypothalamic pituitary adrenal

11β-HSD-2:

11β-hydroxy steroid dehydrogenase-2

MWM:

Morris water maze

PS:

Prenatally stressed

SERT:

Serotonin transporter

SSRI:

Selective serotonin reuptake inhibitor

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  1. Department of Pharmacology, Institute of Drug Research, Hebrew University Medical Centre, Ein Kerem, 91120, Jerusalem, Israel

    Marta Weinstock

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  1. Facultad de Medicina Inst de Biologia Celular y Neurociecias, Universidad de Buenos Aires, Buenos Aires, Argentina

    Marta C. Antonelli

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Weinstock, M. (2015). Changes Induced by Prenatal Stress in Behavior and Brain Morphology: Can They Be Prevented or Reversed?. In: Antonelli, M. (eds) Perinatal Programming of Neurodevelopment. Advances in Neurobiology, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1372-5_1

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