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Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.

ABSTRACT: Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously control for medication usage in the subset of medicated depressed subjects. These analyses yielded a rich profile of dysregulated genes. Two of the most highly dysregulated genes of interest were stresscopin, a neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a transcription factor. Secondary cell-based analysis demonstrated that stresscopin and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These findings identify abnormal gene expression in a discrete region of MDD subjects and contribute to further elucidation of the molecular alterations of this complex mood disorder.

SUBMITTER: Kang HJ 

PROVIDER: S-EPMC3763487 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Gene expression profiling in postmortem prefrontal cortex of major depressive disorder.

Kang Hyo Jung HJ   Adams David H DH   Simen Arthur A   Simen Birgitte B BB   Rajkowska Grazyna G   Stockmeier Craig A CA   Overholser James C JC   Meltzer Herbert Y HY   Jurjus George J GJ   Konick Lisa C LC   Newton Samuel S SS   Duman Ronald S RS  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20071101 48

Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously contr  ...[more]