Comparison of frailty of primary neurons, embryonic, and aging mouse cortical layers

Neurobiol Aging. 2014 Feb;35(2):322-30. doi: 10.1016/j.neurobiolaging.2013.08.005. Epub 2013 Sep 4.


Superficial layers I to III of the human cerebral cortex are more vulnerable toward Aβ peptides than deep layers V to VI in aging. Three models of layers were used to investigate this pattern of frailty. First, primary neurons from E14 and E17 embryonic murine cortices, corresponding respectively to future deep and superficial layers, were treated either with Aβ(1-42), okadaic acid, or kainic acid. Second, whole E14 and E17 embryonic cortices, and third, in vitro separated deep and superficial layers of young and old C57BL/6J mice, were treated identically. We observed that E14 and E17 neurons in culture were prone to death after the Aβ and particularly the kainic acid treatment. This was also the case for the superficial layers of the aged cortex, but not for the embryonic, the young cortex, and the deep layers of the aged cortex. Thus, the aged superficial layers appeared to be preferentially vulnerable against Aβ and kainic acid. This pattern of vulnerability corresponds to enhanced accumulation of senile plaques in the superficial cortical layers with aging and Alzheimer's disease.

Keywords: Aging; Alzheimer's disease; Aβ amyloid; Cell death; Cell viability; Cerebral cortex; Cortical layers; Cortical vulnerability; Cux2; Kainic acid; Okadaic acid; PSD-95.

Publication types

  • Comparative Study

MeSH terms

  • Aging / pathology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / adverse effects
  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Humans
  • Kainic Acid / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects*
  • Neurons / pathology*
  • Okadaic Acid / adverse effects
  • Peptide Fragments / adverse effects
  • Plaque, Amyloid / metabolism


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Okadaic Acid
  • Kainic Acid