Regulators of glucocorticoid receptor function in an animal model of depression and obesity |
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| Authors: | A. Kurek K. Głombik J. Detka A. Basta‐Kaim M. Kubera W. Lasoń B. Budziszewska |
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| Affiliation: | Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland |
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| Abstract: | Obesity is a disease that often co‐occurs with depression and there is some evidence to indicate that chronic stress in the perinatal period, in association with overactive glucocorticoids, can cause permanent changes that increase the risk of the development of both depression and obesity later in life. However, the mechanism responsible for the overly potent action of glucocorticoids in both depression and obesity is not known. The present study aimed to determine the expression of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) and the factors that affect GR function (FKBP51, Bag‐1 and HSP70) in a prenatal stress animal model of depression, a model of obesity and a model of both depression and obesity. Prenatal stress but not high‐fat diet (HFD) was found to decrease the GR concentration in the frontal cortex. The level of the Bag‐1M (46 kDa) isoform was also decreased in this structure but only in prenatal‐stressed animals that did not show depression‐like behaviour in the Porsolt test and were fed the standard diet. In the model of depression employed in the present study, decreases in MR expression and GR co‐chaperone (FKBP51) levels in the hippocampus were also observed and HFD intensified the prenatal stress‐induced changes in MR expression. The results obtained indicated that prenatal stress affected the expression of GRs, MRs and their co‐chaperones in the brain, although its effects were different in the frontal cortex and hippocampus. The decrease in MR density in the hippocampus and increased plasma insulin level appeared to be the most significant changes observed in the model of the co‐occurrence of depression and obesity, which could limit the neuroprotective effects associated with the activation of MR and be a marker of peripheral insulin resistance, respectively. |
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| Keywords: | brain depression glucocorticoid receptors mineralocorticoid receptors obesity |
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