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

Chapter
Part of the Advances in Neurobiology book series (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.

Keywords

Amygdala Antidepressants Anxiety Cognitive deficits Corticotropin-releasing hormone Dorsal hippocampus Gestational stress Glucocorticoids Serotonin 

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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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Pharmacology, Institute of Drug ResearchHebrew University Medical CentreJerusalemIsrael

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