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Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus.

Lan Wei1, Jin Hao, Richard K Lacher

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA.

Developmental Neuroscience
|June 13, 2015
PubMed
Summary

Early-life stress in juvenile mice impairs synaptic development and reduces key proteins for axonal growth and mitochondrial function. This suggests a sequential impact on the developing hippocampus.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Psychiatry

Background:

  • Conflicting reports exist on childhood abuse effects on hippocampal function.
  • Early-life stress (ELS) impacts may manifest in adulthood or childhood.
  • Animal models are crucial for understanding ELS effects on hippocampal development.

Purpose of the Study:

  • To investigate the effects of brief daily separation (BDS), a model of ELS, on juvenile mouse hippocampal development.
  • To characterize molecular and structural changes in the hippocampus during a critical developmental window.
  • To establish a mouse model for studying ELS-induced hippocampal alterations.

Main Methods:

  • Utilized brief daily separation (BDS) in 28-day-old mice as a model for early-life stress.

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  • Quantified hippocampal synaptosome protein content and expression of synaptic proteins using LC-MRM mass spectrometry.
  • Performed Golgi staining to assess dendritic spine morphology in hippocampal CA1 neurons.

    • Main Results:

    • BDS significantly decreased total hippocampal synaptosome protein content in 28-day-old mice.
    • Reduced expression of synaptic, axonal growth, myelination, and mitochondrial proteins was observed.
    • Golgi staining revealed impaired synaptic maturation and pruning, with more immature and fewer mature spines.
    • In younger (14-day-old) pups, BDS affected axonal growth and myelination proteins but not synaptic proteins.

    Conclusions:

    • Brief daily separation (BDS) impairs synaptic maturation and reduces essential proteins for axonal growth, myelination, and mitochondrial function in the juvenile mouse hippocampus.
    • The findings suggest a sequential model where BDS first disrupts axonal growth and myelination, followed by synaptic maturation deficits.
    • This study provides critical insights into the timing and mechanisms of early-life stress effects on hippocampal development.