Microarray analysis of cultured human brain aggregates following cortisol exposure: Implications for cellular functions relevant to mood disorders

Neurobiology of Disease

卷:23

G. Chana¹  M. Altieri²  E. Domenici²  F. Faggioni²  E. Merlo-Pich²  I.P. Everall³  E. Feltrin³  S. Salaria⁴  F. Caldara⁴ 

[1] Corresponding author. Fax: [phone].;

[2] Bioinformatics, Centre of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, 37135 Verona, Italy;

[3] Biology, and Clinical Pharmacology Discovery Medicine, Centre of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, 37135 Verona, Italy,;

[4] Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA;

关键词: Human Fetal Brain Aggregates;    Glucocorticoids;    Gene Expression;    Microarray Analysis;    Fibroblast Growth Factors;    Mood Disorders;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown