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Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats

Abstract

In the learned helplessness (LH) animal model of depression, failure to attempt escape from avoidable environmental stress, LH, indicates behavioral despair, whereas nonhelpless (NH) behavior reflects behavioral resilience to the effects of environmental stress. Comparing hippocampal gene expression with large-scale oligonucleotide microarrays, we found that stress-resilient (NH) rats, although behaviorally indistinguishable from controls, showed a distinct gene expression profile compared to LH, sham stressed, and naïve control animals. Genes that were confirmed as differentially expressed in the NH group by quantitative PCR strongly correlated in their levels of expression across all four animal groups. Differential expression could not be confirmed at the protein level. We identified several shared degenerate sequence motifs in the 3′ untranslated region (3′UTR) of differentially expressed genes that could be a factor in this tight correlation of expression levels among differentially expressed genes.

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Acknowledgements

We thank the staff of the University of Washington Center for Expression Arrays for their expert assistance with our microarray experiments and Gerald Kramer for technical assistance. We would also like to thank the VA Medial Research Service for supporting this study and Daniel R Wilson, MD, Professor and Chair of Psychiatry, Creighton University, for administrative support.

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Correspondence to R Kohen.

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Kohen, R., Kirov, S., Navaja, G. et al. Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats. Pharmacogenomics J 5, 278–291 (2005). https://doi.org/10.1038/sj.tpj.6500322

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