한빛사논문
- 조회1,399
Abstract
M-S Lee1, Y-H Kim1, W-S Park1, O-K Park1, S-H Kwon1, K S Hong2, H Rhim3, I Shim4, K Morita5, D L Wong6, P D Patel7, D M Lyons8, A F Schatzberg8 and S Her1,*
1Bio-Imaging Centre, Korea Basic Science Institute, Chuncheon, South Korea
2Division of MR Research, Korea Basic Science Institute, Cheongwon, South Korea
3Neuroscience Centre, Korea Institute of Science and Technology, Seoul, South Korea
4Acupuncture and Meridian Science Research Centre, Kyung Hee University, Seoul, South Korea
5Department of Nursing, Shikoku University, School of Health Sciences, Tokushima, Japan
6Department of Psychiatry, Harvard Medical School and Laboratory of Molecular and Developmental Neurobiology, McLean Hospital, Belmont, MA, USA
7Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan Medical Centre, Ann Arbor, MI, USA
8Departments of Psychiatry, Stanford University Medical Centre, Stanford, CA, USA
*Correspondence: Dr S Her, Bio-Imaging Centre, Korea Basic Science Institute, 192-1 Hyoja 2-Dong, Chuncheon, Gangwon-Do 200-701, South Korea.
Abstract
Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic?pituitary?adrenal axis activity.
논문정보
- Research article
- 2014년 10월 (BRIC 등록일 2014-10-24)
- 국내(교신)+국외 연구진
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