Gene expression patterns in brain cortex of three different animal models of depression

Abstract

Animal models represent a very useful tool for the study of depressive-like behavior and for the evaluation of the therapeutic efficacy of antidepressants. Nevertheless, gene expression patterns of these different animal models and whether genes classically associated with human major depression are present in these genetic profiles remain unknown. Gene expression was evaluated in three animal models of depression: acute treatment with reserpine, olfactory bulbectomy and chronic treatment with corticosterone. Gene expression analysis was carried out using the Affymetrix GeneChip â technology. The results were evaluated using the GeneChip Operating software (GCOS 1.3) and analyzed with the GENESPRING GX v7.3 bioinformatics software (Agilent) and DCHIP 2005 software. Expression changes were validated with quantitative real-time polymerase chain reaction (RT-PCR) assays. Many transcripts were differentially expressed in the cortex of depressed-like animals in each model. Gene ontology analysis showed that significant gene changes were clustered primarily into functional neurochemical pathways associated with apoptosis and neuronal differentiation. When expression profiles were compared among the three models, the number of transcripts differentially expressed decreased and only two transcripts (complement component 3 and fatty acidbinding protein 7) were differentially expressed in common. Both genes were validated with RT-PCR. Moreover, five (Htr2a, Ntrk3, Crhr1, Ntrk2 and Crh) of the genes classically related to human major depression were differentially expressed in at least one of these models. The different animal models of depression share relevant characteristics although gene expression patterns are different among them. Moreover, some of the classical genes related to human major depression are differentially expressed in these models.

Possible Involvement of Signal Transducers and Activators of Transcription 3 System on Depression in the Model Mice Brain

“…We used the frontal cortex to isolate depression factors since there are many reports on this area related to depression. [17][18][19][20] Recently, the hippocampus also has been noticed about relationship between neurogenesis and depression. 21,22) Therefore, we also examined expression changes of isolated genes in the hippocampus of our model mice.…”

Expression of inflammatory markers in a genetic rodent model of depression

“…A study comparing gene expression patterns in brain cortex of three rat models of depression found only two genes being differentially expressed in common, fatty acid binding protein 7 and complement factor C3. In two of the models, both drug-induced, they observed downregulation of C3, whereas in the third, the olfactory bulbectomy model, upregulation of C3 had occurred, which might be explained by the neuronal injury caused by the surgical procedure [43]. Complement activation involving C3 has been shown to modulate synapse formation during brain development in mice, suggesting that abnormal levels of C3 might lead to aberrantly activated synapse elimination [44].…”

Androgenic Activity Evaluation of Ginger Rhizome inReducing Depression in the Forced Swimming Test of RatsExposed to Electromagnetic Field (EMF)

“…One of the most important ways to identify new antidepressant drugs are animal models (7,8). The most common method used for the detection of antidepressants in animals is forced swimming test (FST) that was proposed primarily (9, 10) and was subsequently improved (6,11).…”