N Drigues1, T Poltyrev, C Bejar, M Weinstock, M B H Youdim. 1. Eve Topf and National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Technion - Faculty of Medicine, Haifa, Israel.
Abstract
BACKGROUND: Chronic antidepressant treatment causes alterations in several hippocampal genes, which participate in neuronal plasticity. However the full picture of their mechanism of action is not known. The advent of genomics enables to identify a broader mechanism of action and identify novel targets for antidepressant development. METHODS: The present study examined the cDNA microarray gene expression profile in the hippocampus induced by chronic antidepressant treatment, in rats exposed to the forced swim test. Animals were treated for 2 weeks with moclobemide, clorgyline and amitriptyline. RESULTS: The three antidepressants significantly reduced immobility in the forced swim test and initiated significant homologous changes in gene expressions. These include up regulation of cAMP response element binding protein and down regulation of corticotrophin releasing hormone. Other gene changes noted were those related to neuropeptides, neurogenesis and synaptogenesis, including synaptophysin and neogenin. Some 89 genes were changed by at least 2 drugs, out of which 53 were changed oppositely by forced swim test. Confirmation of gene changes, have come from real time RT-PCR. CONCLUSIONS: A significant number and homology in gene expression were observed with the three antidepressants. Many of the genes were associated with neurogenesis and synaptogenesis, including synaptophysin and neogenin.
BACKGROUND: Chronic antidepressant treatment causes alterations in several hippocampal genes, which participate in neuronal plasticity. However the full picture of their mechanism of action is not known. The advent of genomics enables to identify a broader mechanism of action and identify novel targets for antidepressant development. METHODS: The present study examined the cDNA microarray gene expression profile in the hippocampus induced by chronic antidepressant treatment, in rats exposed to the forced swim test. Animals were treated for 2 weeks with moclobemide, clorgyline and amitriptyline. RESULTS: The three antidepressants significantly reduced immobility in the forced swim test and initiated significant homologous changes in gene expressions. These include up regulation of cAMP response element binding protein and down regulation of corticotrophin releasing hormone. Other gene changes noted were those related to neuropeptides, neurogenesis and synaptogenesis, including synaptophysin and neogenin. Some 89 genes were changed by at least 2 drugs, out of which 53 were changed oppositely by forced swim test. Confirmation of gene changes, have come from real time RT-PCR. CONCLUSIONS: A significant number and homology in gene expression were observed with the three antidepressants. Many of the genes were associated with neurogenesis and synaptogenesis, including synaptophysin and neogenin.
Authors: Patrícia Patrício; António Mateus-Pinheiro; Martin Irmler; Nuno D Alves; Ana R Machado-Santos; Mónica Morais; Joana S Correia; Michal Korostynski; Marcin Piechota; Rainer Stoffel; Johannes Beckers; João M Bessa; Osborne F X Almeida; Nuno Sousa; Luísa Pinto Journal: Neuropsychopharmacology Date: 2014-07-18 Impact factor: 7.853