Abstract：
:Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity is thought to be an important factor in pathogenesis of depression. In animals, stress or glucocorticoids given in prenatal period lead to long-lasting behavioral and neuroendocrine changes similar to those observed in depressed patients. However, molecular basis for HPA disturbances in animals exposed to prenatal stress - a model of depression - have been only partially recognized. Therefore, in the present study we investigated the effect of prenatal stress on behavioral changes, blood corticosterone level, concentrations of glucocorticoid receptor (GR) and its cochaperone, FKBP51, in the hippocampus and frontal cortex in adult rats. It has been found that prenatally stressed rats display high level of immobility in the Porsolt test and anxiety-like behavior. The HPA axis hyperactivity in theses animals was evidenced by corticosterone hypersecretion at the end of the light phase and 1h following acute stress. Western blot study revealed that GR level was significantly elevated in the hippocampus but not in the frontal cortex of prenatally stressed rats, whereas concentration of FKBP51 was decreased only in the former brain structure. Chronic treatment with imipramine, fluoxetine, mirtazapine and tianeptine have diminished both behavioral and biochemical alterations observed in this animal model of depression. These data indicate that the increase in hippocampal GR level and low concentration of FKBP51 in the frontal cortex may be responsible for enhanced glucocorticoid action in depression.
journal_name
Psychoneuroendocrinologyjournal_title
Psychoneuroendocrinologyauthors
Szymańska M,Budziszewska B,Jaworska-Feil L,Basta-Kaim A,Kubera M,Leśkiewicz M,Regulska M,Lasoń Wdoi
10.1016/j.psyneuen.2008.12.012subject
Has Abstractpub_date
2009-07-01 00:00:00pages
822-32issue
6eissn
0306-4530issn
1873-3360pii
S0306-4530(08)00338-7journal_volume
34pub_type
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