title: Altered response to mirtazapine on gene expression profile of lymphocytes from Alzheimer's patients.
abstract: Antidepressants are widely used in the treatment of mood disorders associated with dementia, however little information is available on their effect at the molecular level. We have demonstrated that gene expression profiles of lymphocytes from patients with Alzheimer dementia differ from that seen with controls, with alpha(2)-adrenoceptor being the most highly repressed transcript. To address this issue in light of antidepressant treatment, we used lymphocytes derived from Alzheimer patients and control individuals to assess the impact of mirtazapine, the novel antidepressant with alpha(2)-adrenoceptor antagonistic activities, on gene expression using a cDNA microarray representing 3200 distinct human genes. Sequences that are differentially regulated after treatment with mirtazapine were identified and categorized based on similarities in biological functions. This analysis revealed that selected biological processes, including protein metabolism, cytoskeleton integrity, immune response, cellular plasticity, and neurotransmission, are involved in early phases of administration of this antidepressant. In addition, although it was possible to identify common targets, the expression profiles of Alzheimer lymphocytes differed mainly in their magnitude from those seen with controls. These results confirm the usefulness of the gene array approach for studying Alzheimer-specific changes in the periphery and suggest that the expression of genes of Alzheimer lymphocytes is modulated differently by mirtazapine, which correlates with the pathology.
authors.affiliation: Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721 Szeged, Semmelweis u. 6, Hungary. palotas@nepsy.szote.u-szeged.hu
authors.forename: András
authors.initials: A
authors.lastname: Palotás
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.forename: Klára
authors.initials: K
authors.lastname: Kitajka
authors.forename: Miklós
authors.initials: M
authors.lastname: Palotás
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000078785:Mirtazapine; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine