Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders.
Increased cortisol levels in humans are often observed in patients suffering from mood disorders. In this study human fetal brain aggregates were exposed to cortisol at 500 nM for 3 weeks, as an in-vitro model of chronic cortisol exposure. Microarray analysis on extracted mRNA using the Affymetrix U133A platform was then performed. Our results demonstrated a significant effect of cortisol on 1648 transcripts; 736 up-regulated and 912 down-regulated genes. The most differentially regulated biological categories were: RNA processing, protein metabolism, and cell growth. Within these categories we observed a down-regulation of fibroblast growth factor 2 (FGF2) (-1.5-fold) and aquaporin4 (AQP4) (-1.7-fold), alongside an up-regulation of fibroblast growth factor 9 (FGF9) (+1.7-fold) and vesicle associated membrane protein2 (VAMP2) (+1.7-fold). FGF2, FGF9, AQP4 and VAMP2 changes were confirmed at the protein level by immunohistochemistry. Alterations in FGF transcripts are in keeping with recent literature demonstrating such effects in patients with mood disorders.
Salaria
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S
Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA. ssalaria@ucsd.edu
Chana
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Caldara
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Feltrin
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Altieri
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Faggioni
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Domenici
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Merlo-Pich
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Everall
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IP
D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
D006133:Growth Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D006854:Hydrocortisone