Animal Models of Early-Life Adversity

Methods Mol Biol. 2019:2011:143-161. doi: 10.1007/978-1-4939-9554-7_10.

Abstract

From the prenatal period throughout the first years of life, the brain undergoes its most rapid development, a period during which it is highly sensitive to external experiences. The timing of brain development differs from one region to another, as it also differs between substrates, neurotransmitter systems, and central endocrine circuitries. These discontinuities are part of the "critical periods of brain development." Early-life adversity (ELA), such as exposure to infection, maternal deprivation, and substance use, disrupts the programmed brain development, yielding a myriad of deviations in brain circuitry, stress responsivity, cognitive function, and general health. This is applicable to both humans and animal models.In our laboratory, several experimental animal designs have been developed that allow investigating the long-lasting consequences of ELA on brain function, cognitive and emotional development, and the risk to develop stress-related psychopathology later in adulthood. This book chapter will provide a review of such animal models, in particular, designs related to infections (LPS-induced), the quality of mother-infant relationship (maternal deprivation and separation), and substance use (ethanol intoxication). The behavior tests, biochemical, and immunohistochemistry assays applied after ELA will be explained. The behavioral tests encompass the open-field, elevated plus maze, forced swim, sucrose preference, Y-maze, object recognition, and Morris water maze tests. These experiments allow the assessment of several outcomes of interest, pertaining to locomotor activity, anxiety-like symptoms, depressive-like symptoms, working memory, recognition memory, spatial memory, and learning performance. The biochemical assays are employed to measure the level of oxidative stress and inflammation in brain areas after application of adversity. Immunohistochemistry puts into perspective the degree of immunoreactivity in the brain subjected to adversity. The findings from our laboratory indicate that the nature and timing of exposure play a critical role in sensitivity to develop neurodevelopmental disorders.

Keywords: Behavioral tests; Biochemical assays; Early-life adversity; Immunohistochemistry; Neurodevelopmental disorders.

MeSH terms

  • Animals
  • Behavior, Animal
  • Biomarkers
  • Brain / growth & development*
  • Brain / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Growth and Development*
  • Immunohistochemistry
  • Maze Learning
  • Neuroglia / metabolism
  • Stress, Physiological*
  • Stress, Psychological*

Substances

  • Biomarkers