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Comprehensive expression analysis of a rat depression model

The Pharmacogenomics Journal volume 4, pages 114–126 (2004)Cite this article

ABSTRACT

Herein we report on a large-scale analysis of gene expression in the ‘learned helplessness’ (LH) rat model of human depression, using DNA microarrays. We compared gene expression in the frontal cortex (FC) and hippocampus (HPC) of untreated controls, and LH rats treated with saline (LH-S), imipramine or fluoxetine. A total of 34 and 48 transcripts were differentially expressed in the FC and HPC, respectively, between control and LH-S groups. Unexpectedly, only genes for NADH dehydrogenase and zinc transporter were altered in both the FC and HPC, suggesting limited overlap in the molecular processes from specific areas of the brain. Principal component analysis revealed that sets of upregulated metabolic enzyme genes in the FC and downregulated genes for signal transduction in the HPC can distinguish clearly between depressed and control animals, as well as explain the responsiveness to antidepressants. This comprehensive data could help to unravel the complex genetic predispositions involved in human depression.

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Abbreviations

BDNF:

brain-derived neurotrophic factor

EST:

expressed sequence tag

FC:

frontal cortex

HPC:

hippocampus

IS:

inescapable shocks

LH:

learned helplessness

LH-F:

LH rats treated with fluoxetine

LH-I:

LH rats treated with imipramine

LH-S:

LH rats treated with saline

NMDA:

N-methyl-D-aspartate

NREM:

nonrapid eye movement

PKC:

protein kinase C

RT:

reverse transcription

SSRI:

selective serotonin reuptake inhibitor

TCA:

tricyclic antidepressant

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Acknowledgements

We would like to thank Shuichi Tsutsumi and Hiroko Meguro for assistance with microarray data analysis, Yuichi Ishitsuka, Yuki Iijima and Shin-ichi Ohno for help with animal experiments, Kazuo Yamada for useful comments and Joanne Meerabux for critical reading of this manuscript. This study was partly supported by Grants-in-Aid for Young Scientists (B) (No. 13770566) from the Ministry of Education, Culture, Sports and Technology (MEXT).

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Authors and Affiliations

  1. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan

    N Nakatani, H Aburatani, J Semba & T Yoshikawa

  2. Department of Cancer Systems Biology, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    H Aburatani

  3. Department of Information Systems, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    K Nishimura

  4. The University of the Air, Chiba, Japan

    J Semba

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  1. N Nakatani
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Correspondence to T Yoshikawa.

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Supplementary Information accompanies the paper on The Pharmacogenomics Journal website (http://www.nature.com/tpj).

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Nakatani, N., Aburatani, H., Nishimura, K. et al. Comprehensive expression analysis of a rat depression model. Pharmacogenomics J 4, 114–126 (2004). https://doi.org/10.1038/sj.tpj.6500234

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