Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis

Biol Psychiatry. 2006 May 1;59(9):786-92. doi: 10.1016/j.biopsych.2005.11.009. Epub 2006 Feb 7.


Background: Prenatal stress constitutes a developmental risk factor for later psychopathology. The behavioral disorders are sustained by neurobiological alterations including long-term reduction of hippocampal neurogenesis; its deregulation has been involved in cognitive impairments, mood disorders and addiction. A major goal is to define periods in development and strategies for intervening to prevent the effects of early stressful events. We investigated the ability of a postnatal infantile stimulation to prevent prenatal stress-induced alteration in hippocampal neurogenesis.

Methods: The influence of postnatal handling on prenatal stress-induced changes in hippocampal neurogenesis was examined in 4 and 26 month-old male rats. Three distinct phases of the neurogenesis were studied: proliferation, survival and neuronal differentiation.

Results: Prenatal stress reduced hippocampal cell proliferation all throughout life. Furthermore, the survival rate of newborn cells, the number of immature neurons and the number of differentiated new neurons were reduced in young and old prenatally-stressed rats. All those deleterious effects were counteracted by neonatal handling.

Conclusions: These data show that finer aspects of brain shaping can be rewired by environmental influences occurring at sensitive phase of development. They also suggest that infantile stimulation may reverse the appearance of behavioral disorders induced by early life stress.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Proliferation
  • Cell Survival / physiology
  • Doublecortin Domain Proteins
  • Female
  • Handling, Psychological*
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Immunohistochemistry / methods
  • Ki-67 Antigen / metabolism
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Organogenesis / physiology
  • Phosphopyruvate Hydratase / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Sialic Acids / metabolism
  • Stress, Psychological / complications
  • Stress, Psychological / pathology*


  • Doublecortin Domain Proteins
  • Ki-67 Antigen
  • Microtubule-Associated Proteins
  • Neural Cell Adhesion Molecule L1
  • Neuropeptides
  • Sialic Acids
  • polysialyl neural cell adhesion molecule
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine