The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress
Abstract
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of ...nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.
Keywords:
nuclear glucocorticoid receptor / psychosocial stressSource:
Russian Journal of Physical Chemistry A, 2011, 85, 13, 2422-2425Funding / projects:
- Defining a cluster of molecular biomarkers for improved diagnostics and therapy of mood disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41029)
DOI: 10.1134/S0036024411130152
ISSN: 0036-0244
WoS: 000297922700032
Scopus: 2-s2.0-85031406254
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VinčaTY - JOUR AU - Mitić, Miloš AU - Simić, Iva AU - Đorđević, Jelena D. AU - Radojčić, Marija AU - Adžić, Miroslav PY - 2011 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4604 AB - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study. T2 - Russian Journal of Physical Chemistry A T1 - The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress VL - 85 IS - 13 SP - 2422 EP - 2425 DO - 10.1134/S0036024411130152 ER -
@article{ author = "Mitić, Miloš and Simić, Iva and Đorđević, Jelena D. and Radojčić, Marija and Adžić, Miroslav", year = "2011", abstract = "Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.", journal = "Russian Journal of Physical Chemistry A", title = "The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress", volume = "85", number = "13", pages = "2422-2425", doi = "10.1134/S0036024411130152" }
Mitić, M., Simić, I., Đorđević, J. D., Radojčić, M.,& Adžić, M.. (2011). The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress. in Russian Journal of Physical Chemistry A, 85(13), 2422-2425. https://doi.org/10.1134/S0036024411130152
Mitić M, Simić I, Đorđević JD, Radojčić M, Adžić M. The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress. in Russian Journal of Physical Chemistry A. 2011;85(13):2422-2425. doi:10.1134/S0036024411130152 .
Mitić, Miloš, Simić, Iva, Đorđević, Jelena D., Radojčić, Marija, Adžić, Miroslav, "The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress" in Russian Journal of Physical Chemistry A, 85, no. 13 (2011):2422-2425, https://doi.org/10.1134/S0036024411130152 . .