Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat

Abstract

There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase); with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.

A Randomized Trial on Mineralocorticoid Receptor Blockade in Men: Effects on Stress Responses, Selective Attention, and Memory

“…Several MR and GR gene variants were found in association with psychopathology and responsiveness to antidepressants, as well as with altered cognitive performance Klok et al, 2010;Kuningas et al, 2007;Spijker and van Rossum, 2009). Furthermore, it has been proposed that reduced functionality of MRs relative to GRs may predispose to depression (de Kloet et al, 2005;Reul et al, 2000), while antidepressants might restore the balance between the two receptor types (Bjartmar et al, 2000;Mason and Pariante, 2006;Reul et al, 1993;Seckl and Fink, 1992). Additional support for a role of MR in depression comes from data showing that an MR antagonist inhibits the clinical efficacy of antidepressant treatment (Holsboer, 1999), from a study showing acceleration of antidepressant effects through MR stimulation (Otte et al, 2010) and indications for MR dysfunction in treatment-resistant depression (Juruena et al, 2010).…”

St John's wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response

“…Specific effects of antidepressants or electroconvulsive treatment have already been reported for immediate early genes and transcription factors such as c-fos, zif268, NGF1-A, phosphorylation of CRE-binding protein, DfosB, and Narp. [65][66][67][68][69][70][71][72] In our analysis, we identified four genes that were downregulated in response to both IMI and SJW. Such genes could be potential markers for predicting response to antidepressant treatment; however, the fact that genes are coordinately downregulated suggests there are specific combinations of transcriptional regulators that control the expression of these four genes.…”

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

“…NGFI-A (alias Egr1, zif268, krox24, ZENK) has been shown to be up-regulated following chronic treatment with a variety of different antidepressants (Bjartmar et al 2000) and is another candidate on our list of genes regulated by chronic paroxetine application. Alterations in NGFI-A expression have been observed in different brain regions and seem to be responsive to a variety of stimuli (e.g., Thompson and Rosen 2006).…”