Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression
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Open Access
- 18 May 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 16 (7), 751-762
- https://doi.org/10.1038/mp.2010.52
Abstract
The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (n=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction], P<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.Keywords
This publication has 65 references indexed in Scilit:
- The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression.2008
- Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depressionMolecular Psychiatry, 2007
- Disruption of cerebral cortex MET signaling in autism spectrum disorderAnnals of Neurology, 2007
- Innate Immunity and Protective Neuroinflammation: New Emphasis on the Role of Neuroimmune Regulatory ProteinsInternational review of neurobiology, 2007
- Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophreniaMolecular Psychiatry, 2007
- Corticotropin-releasing factor test in melancholic patients in depressed state versus recovery: A comparative studyProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2007
- Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depressionProceedings of the National Academy of Sciences, 2005
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory responseBlood, 2005
- Different immune patterns in melancholic and non-melancholic major depressionArchiv Fur Psychiatrie Und Nervenkrankheiten, 2001