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Original Research ARTICLE

Front. Psychiatry, 25 April 2011 | http://dx.doi.org/10.3389/fpsyt.2011.00018

Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect

Kelly A. Bordner1, Elizabeth D. George1, Becky C. Carlyle1, Alvaro Duque2, Robert R. Kitchen1,3, TuKiet T. Lam4, Christopher M. Colangelo4, Kathryn L. Stone4, Thomas B. Abbott4, Shrikant M. Mane4, Angus C. Nairn1 and Arthur A. Simen1*
  • 1 Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
  • 2 Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA
  • 3 Department of Physics, The University of Edinburgh, Scotland, UK
  • 4 Department of Molecular Biophysics and Biochemistry/Keck Biotechnology Services, New Haven, CT, USA

Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior.

Keywords: early life neglect, microarray analysis, proteomic analysis, RNA-sequencing, prefrontal cortex, oligodendrocytes, translation

Citation: Bordner KA, George ED, Carlyle BC, Duque A, Kitchen RR, Lam TT, Colangelo CM, Stone KL, Abbott TB, Mane SM, Nairn AC and Simen AA (2011) Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect. Front. Psychiatry 2:18. doi: 10.3389/fpsyt.2011.00018

Received: 21 February 2011; Accepted: 11 April 2011;
Published online: 25 April 2011.

Edited by:

Mark Reimers, Virginia Commonwealth University, USA

Reviewed by:

Rafael Fernández-Chacón, The Neuroscience Institute at Seville, Spain
Jessica Connelly, University of Virginia, USA

Copyright: © 2011 Bordner, George, Carlyle, Duque, Kitchen, Lam, Colangelo, Stone, Abbott, Mane, Nairn and Simen. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Arthur A. Simen, Divisions of Molecular Psychiatry, Human Genetics, and Aging Research, Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT 06511-6624, USA. e-mail: arthur.simen@yale.edu