The role of genes involved in stress, neural plasticity, and brain circuitry in depressive phenotypes: Convergent findings in a mouse model of neglect

Behav Brain Res. 2016 Dec 15:315:71-4. doi: 10.1016/j.bbr.2016.08.010. Epub 2016 Aug 6.


Early life neglect increases risk for the development of psychopathologies during childhood and adulthood, including depression and anxiety disorders. We recently reported epigenetic changes in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3 (ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting Protein (TPPP). To validate the role of these genes in depression risk, secondary analyses were conducted of gene expression data obtained from medial prefrontal cortex (mPFC) tissue of mice subjected to a model of maternal neglect which included maternal separation and early weaning (MSEW). Anxiety and depression-like phenotype data derived using the elevated plus maze (EPM) and forced swimming test (FST), respectively, were also available for secondary analyses. Behavioral tests were conducted in MSEW and control adult male mice when they were between 65 and 80days old. ID3, GRIN1 and TPPP gene expression in the mPFC were found to significantly predict behavioral differences in the EPM and FST. These results further support the role of these genes in the etiology of depressive and anxiety phenotypes following early life stress.

Keywords: DNA-binding protein inhibitor ID-3 (ID3); Depression; Glutamate NMDA receptor (GRIN1); Methylation; Neglect; Tubulin polymerization promoting protein (TPPP).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Depression / pathology*
  • Disease Models, Animal
  • Gene Expression Regulation / physiology*
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / metabolism
  • Male
  • Maternal Deprivation*
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Microarray Analysis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / physiology*
  • Prefrontal Cortex / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Stress, Psychological / pathology*
  • Swimming / psychology


  • Gprin1 protein, mouse
  • Inhibitor of Differentiation Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • TPPP protein, mouse
  • Idb3 protein, mouse