Stress Type Dependence of Expression and Cytoplasmic-Nuclear Partitioning of Glucocorticoid Receptor, Hsp90 and Hsp70 in Wistar Rat Brain

Abstract

Chronic exposure to stress is associated with different behavioral and neurological syndromes including impaired excitability of nerve cells in hippocampus (HIPPO) and prefrontal cortex (PFC), regions of the brain that are important for adaptation. The successful adaptation to stress involves negative feedback at the level of the hypothalamic-pituitary-adrenal (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 significant decrease in serum corticosterone (CORT), probably due to alterations in the GR signaling pathway. We exploited 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 translocated to the nucleus in both brain structures. Under chronic stress, when CORT was below the control level, GR was retained in the cytoplasm of PFC, and evenly distributed between 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 protein expression and cytoplasmic-nuclear partitioning of the GR, Hsp90 and Hsp70 proteins may be related to maladaptive response of the HPA axis under chronic stress.