engleski

Gender difference in glucocorticoid, insulin and estrogen receptors expression upon chronic stress and aging

Introduction: Insulin and estrogen signaling have been associated to molecular mechanisms of neurodegeneration. Changes in those signalling pathways as well as loss of memory are expected upon stress and aging. In this study, expression of estrogen (ER), insulin (IR) and glucocorticoid (GR) receptors was analyzed. Methods: Male and female rats were divided in young and old animal groups. Chronic stress protocol was performed for 10 weeks. Expression of ER-α, IR-β and GR was screened by Western-blotting in hippocampi (HIP) and cerebella (CER). The Statistica software was used for data analysis. Results: Chronic stress caused a decrease of GR in CER of all animal groups, no changes in HIPP of all male groups and a decrease of GR in HIP of all female groups. ER-α expression was increased in CER of all animals with statistical significance reached in case of young males (p=0.049). ER-α in HIP increased in all animal groups except for old males. IR-β expression in CER increased in young males and old females and decreased in old males and young females upon stress. IR-β in HIP increased in all young animals upon stress. Discussion and Conclusion: GR is a transcription factor which adapts the power of stress response. When decreased as in stressed animals, glucose levels in blood decrease and cause low metabolism rate in all cells which is crucial for neuronal survival as well. Estrogen provides neuroprotection and the study shows young males are most affected by ER changes caused by stress. Increased insulin increases the insulin sensitivity and the animals cope better with stress. If IR is decreased, as in all old animals in HIPP, it could be a sign of decompensational mechanisms that leads to neurodegeneration. Previously we observed memory impairment in old females which can be connected to these signalling pathways. Acknowledgments: This study has been funded by Croatian Science Foundation (IP-09-2014- 2324) and Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program and the RECOOP HST Association. Part of this study was performed at the Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, under the supervision of prof. Robert Gaspar. Ethical Committee Approval: Experiments were carried out at Animal Facility of Faculty of Medicine Osijek and was approved under class number 602-04/14-08/06 and registration number 2158-61-07-14-118 and Animal Facility of Faculty of Pharmacy, Szeged, approval number: CSI/01/3796- 7/2015.

stress ; aging ; neurodegeneration ; insulin ; estrogen ; glucocorticoid receptor

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