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PMID: 16484373 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 9 ·2006-02-28 ·Pages 3480-5

Weaver IC, Meaney MJ, Szyf M

Abstract

Early-life experience has long-term consequences on behavior and stress responsivity of the adult. We previously proposed that early-life experience results in stable epigenetic programming of glucocorticoid receptor gene expression in the hippocampus. The aim of this study was to examine the global effect of early-life experience on the hippocampal transcriptome and the development of stress-mediated behaviors in the offspring and whether such effects were reversible in adulthood. Adult offspring were centrally infused with saline vehicle, the histone deacetylase inhibitor trichostatin A (TSA), or the essential amino acid l-methionine. The animals were assessed in an unfamiliar open-field arena, and the hippocampal transcriptome of each animal was evaluated by microarray analysis. Here we report that TSA and methionine treatment reversed the effect of maternal care on open-field behavior. We identified >900 genes stably regulated by maternal care. A fraction of these differences in gene expression is reversible by either the histone deacetylase inhibitor TSA or the methyl donor l-methionine. These results suggest that early-life experience has a stable and broad effect on the hippocampal transcriptome and anxiety-mediated behavior, which is potentially reversible in adulthood.

MeSH Terms
Aging/genetics,physiology,psychology Animals Anxiety/genetics,psychology Behavior, Animal/physiology Cell Adhesion Molecules, Neuronal/genetics DNA Helicases/genetics Extracellular Matrix Proteins/genetics Gene Expression Regulation/drug effects Hippocampus/drug effects,metabolism Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Hydroxamic Acids/pharmacology Maternal Behavior/physiology Methionine/pharmacology Mothers Nerve Tissue Proteins/genetics Proteins/genetics Rats Reelin Protein Serine Endopeptidases/genetics Transcription, Genetic/genetics
Chemicals
Cell Adhesion Molecules, Neuronal Extracellular Matrix Proteins Histone Deacetylase Inhibitors Hydroxamic Acids Nerve Tissue Proteins Proteins Reelin Protein Vof16 protein, rat trichostatin A Methionine Serine Endopeptidases Histone Deacetylases DNA Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Weaver Ian C G
Douglas Hospital Research Center, Montréal, QC, Canada.
Meaney Michael J
Szyf Moshe
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0507526103
Published
2006-02-28
Epub
2006-00-16
Pages
3480-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1413873
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0507526103 PMC Full Text View journal details
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