Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuropsychobiology 2009;59:213–221 DOI: 10.1159/000223733 Stress Type Dependence of Expression and Cytoplasmic-Nuclear Partitioning of Glucocorticoid Receptor, Hsp90 and Hsp70 in Wistar Rat Brain Ana Djordjevic Miroslav Adzic Jelena Djordjevic Marija B. Radojcic Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, Belgrade, Serbia tained in the cytoplasm of PFC, and evenly distributed be- tween compartments in HIPPO. Simultaneously, heat shock proteins partitioning in HIPPO seemed to be mainly stress type-independent, while that of PFC was dependent on stress type. Thus, the stress type-specific responses of GR and heat shock proteins were mainly detected in PFC rather than in HIPPO of Wistar rats. The observed alterations in pro- tein expression and cytoplasmic-nuclear partitioning of the GR, Hsp90 and Hsp70 proteins may be related to maladap- tive response of the HPA axis under chronic stress. Copyright © 2009 S. Karger AG, Basel Introduction The hypothalamic-pituitary-adrenal (HPA) axis plays a primary physiological role in the response to stress and restoration of system homeostasis. Glucocorticoids (GCs), as the final effectors of HPA axis activation, are involved in the regulation of its activity by exerting negative feed- back on several brain structures including the hippocam- pus (HIPPO) and prefrontal cortex (PFC) [1–5] . Abnor- mal GC secretion has been described in several psychiat- Key Words Stress  Hippocampus  Prefrontal cortex  Corticosterone  Glucocorticoid receptor  Heat shock protein 90  Heat shock protein 70 Abstract Chronic exposure to stress is associated with different be- havioral and neurological syndromes including impaired ex- citability of nerve cells in hippocampus (HIPPO) and prefron- tal cortex (PFC), regions of the brain that are important for adaptation. The successful adaptation to stress involves neg- ative feedback at the level of the hypothalamic-pituitary-ad- renal (HPA) axis provided by the glucocorticoid receptor (GR), which is a steroid-dependent transcription factor found in a heterocomplex with heat shock proteins Hsp90 and Hsp70. In Wistar rats, chronic social isolation leads to a sig- nificant decrease in serum corticosterone (CORT), probably due to alterations in the GR signaling pathway. We exploit- ed this type of stress, alone or in combination with acute immobilization, to define changes in the expression level and compartmental distribution of GR, Hsp90 and Hsp70 in HIPPO and PFC. The results indicated that in acute and combined stress, when CORT was increased, GR was translo- cated to the nucleus in both brain structures. Under chronic stress, when CORT was below the control level, GR was re- Received: July 17, 2008 Accepted after revision: March 22, 2009 Published online: June 10, 2009 Marija Radojcic Department of Molecular Biology and Endocrinology VINCA Institute of Nuclear Sciences, PO Box 522-MBE090 RS–11001 Belgrade (Serbia) Tel. +381 11 245 8222, ext. 1304, Fax +381 11 245 5561, E-Mail marija@vin.bg.ac.yu © 2009 S. Karger AG, Basel 0302–282X/09/0594–0213$26.00/0 Accessible online at: www.karger.com/nps A. Djordjevic and M. Adzic contributed equally.