Neurotoxicity Research

, Volume 3, Issue 1, pp 65–83

Long term neurodevelopmental and behavioral effects of perinatal life events in rats

  • Muriel Koehl
  • Valérie Lemaire
  • Monique Vallée
  • Nora Abrous
  • Pier Vincenzo Piazza
  • Willy Mayo
  • Stefania Maccari
  • Michel le Moal
Article

DOI: 10.1007/BF03033231

Cite this article as:
Koehl, M., Lemaire, V., Vallée, M. et al. neurotox res (2001) 3: 65. doi:10.1007/BF03033231

Abstract

Modern neurosciences are now able to open new avenues concerning an experimental approach to clinical neurosciences and psychiatry. Detection and prediction of potential vulnerabilities such as behavioral disturbances and neurodegenerative diseases, are urgent tasks leading to prevention that must be encouraged in parallel to the enormous efforts displayed for treatments. Besides possible genetic origins of diseases, environmental factors are now coming under scrutiny, and especially deleterious and challenging life events and stress occurring during prenatal and postnatal critical periods may orient brain functions towards deleterious developments. The hypothesis that will be examined is that early events might be at the origin of pathological transformations and symptoms after long periods of apparent normal abilities and behavioral homeostasis. We used models of prenatal stress and postnatal manipulations such as cross-fostering. It will be demonstrated that such events induce long-term changes, cognitive and emotional modifications appearing first, when offspring are adults, followed by cognitive defects later in life. Increased sensitivity of the hypothalamic pituitary-adrenal axis (HPA), the endocrine system controlling the secretion of stress hormones (corticoids), appears to be a major element of pathogenesis. HPA axis dysfunction appears very early after birth (3 days) and lasts for months. Cumulative exposure to high levels of hormones seems to be detrimental for some brain regions, especially the hippocampus and major neurotransmitters systems such as dopamine neurons. We evidenced that neuronal modifications in hip-pocampal region are correlated with behavioral and cognitive defects, relating environment, stress in early life, hormonal changes, long-term neuropatho-logical processes and impaired cognition in aging. Moreover appears in offspring, when adults, a proneness to engage in drug dependence. These data emphasize the need to consider early environmental life events as etiological factors for delayed neuropsychiatric disturbances, neurodegenerative defects included. Moreover, they strengthen the interest for a longitudinal approach to promote experimental psychopathology.

Copyright information

© Springer 2001

Authors and Affiliations

  • Muriel Koehl
    • 1
  • Valérie Lemaire
    • 1
  • Monique Vallée
    • 1
  • Nora Abrous
    • 1
  • Pier Vincenzo Piazza
    • 1
  • Willy Mayo
    • 1
  • Stefania Maccari
    • 2
  • Michel le Moal
    • 2
  1. 1.Laboratoire de Psychobiologie des Comportements Adaptatifs — INSERM U.259Université Victor Ségalen Bordeaux 2, Institut François MagendieBordeaux CedexFrance
  2. 2.Laboratoire de Neurosciences du ComportementUniversité Lille 1Villeneuve d’ Ascq CedexFrance