The International Journal of Neuropsychopharmacology



Gene expression profile analysis of the rat cortex following treatment with imipramine and citalopram


Miklós Palotás a1a2, András Palotás a1a2a3c1, László G. Puskás a4, Klára Kitajka a5, Magdolna Pákáski a2, Zoltán Janka a1, József Molnár a6, Botond Penke a3 and János Kálmán a1
a1 Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary
a2 Alzheimer's Disease Research Center, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Faculty of Medicine, University of Szeged, H-6720 Szeged, Somogyi B u. 4, Hungary
a3 Department of Medical Chemistry, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Faculty of Medicine, University of Szeged, H-6721 Szeged, Dóm tér 8, Hungary
a4 Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, H-6701 Szeged, PO Box 521, Hungary
a5 Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, H-6701 Szeged, PO Box 521, Hungary
a6 Department of Microbiology, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Faculty of Medicine, University of Szeged, H-6721 Szeged, Dóm tér 10-11, Hungary

Article author query
palotas m   [PubMed][Google Scholar] 
palotas a   [PubMed][Google Scholar] 
puskas lg   [PubMed][Google Scholar] 
kitajka k   [PubMed][Google Scholar] 
pakaski m   [PubMed][Google Scholar] 
janka z   [PubMed][Google Scholar] 
molnar j   [PubMed][Google Scholar] 
penke b   [PubMed][Google Scholar] 
kalman j   [PubMed][Google Scholar] 

Abstract

The effect of antidepressants is the culmination of a series of molecular actions occurring in the brain. These events are thought to lead to changes in the expression level of numerous, but as yet unknown genes that result in different cellular functions. In our present study we addressed this issue by establishing gene expression profiles of the rat brain after treatment with imipramine and citalopram at therapeutic doses. After 96 h and 4 wk, fronto-temporal cortices from controls and each treated strain were prepared and total RNA was isolated, and assessed using a cDNA microarray system containing 3200 clones. The expression of 6 genes was decreased and 8 were over-expressed by imipramine, whereas 27 were repressed and 7 were up-regulated by citalopram. Members of signal transduction (e.g. phosphatidylinositol transfer protein), structural elements (e.g. tubulin, fibronectin), factors related to protein metabolism in general (e.g. proteasomal subunits, ubiquitin-like proteins, polyadenylation sites), components involved in cell survival (e.g. midkine, stress-inducible protein), and determinants of membrane conductance and ion transport (e.g. vacuolar H+-ATPase), and basics of nuclear functions (e.g. translin, basal transcription factor 3), were some of the genes with altered expression. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signalling, survival and protein metabolism. Our results demonstrate for the first time that antidepressants specifically regulate neuronal plasticity through induction of a highly specific transcriptional programme in brain cells.

(Received October 29 2003)
(Reviewed January 11 2004)
(Revised January 16 2004)
(Accepted February 8 2004)


Key Words: Antidepressant; depression; gene expression; microarray; neuronal plasticity.

Correspondence:
c1 Dr A. Palotás, University of Szeged, H-6720 Szeged, Pécsi u. 4, Hungary. Tel.: +(36) (30)255-6225 Fax: +(36) (62)545-701 E-mail: palotas@nepsy.szote.u-szeged.hu