Brain Glucocorticoid Receptor and Heat Shock Protein 70 Levels in Rats Exposed to Acute, Chronic or Combined Stress

Abstract

The pattern and intensity of glucocorticoid receptor (GR) and heat shock 70 protein (Hsp 70) changes in the hippocampus and brain cortex of adult Wistar rat males exposed to acute (immobilization, cold) and chronic (social isolation, crowding, daily swimming) stress or their combinations were followed by Western immunoblotting. Plasma ACTH and CORT were measured by chemiluminescent method and RIA. A significant decrease in cytosol GR and Hsp 70 was observed after acute stress, while chronic stresses led to negligible changes in both these proteins and caused a reduced responsiveness to a novel acute stress. This was valid irrespective of the type of chronic or acute stress combinations for both hippocampal and cortical GR and Hsp 70. The results support the hypothesis that chronic stress-induced deregulation of the LHPA axis may be caused, at least in part, by partial disruption of intracelullar negative feedback control in the higher centers of the brain.

Expression of heat shock protein 70 in the liver of extensively and intensively kept heavy pigs

“…A significant decrease in the levels of HSP70, one of the most important HSPs, was reported in the liver of acutely stressed male rats, whereas only a weak decrease in the levels of HSP70 was demonstrated in chronic stress models (Filipović et al, 2008). Moreover, the overexpression of HSP70 in the stomach of male rats seemed to protect against gastric ulcers, through its cytoprotective effects on the gastric mucosa, by increasing mucosal blood flow (Shichijo et al, 2003).…”

“…In mammals, the constitutive HSP family members (HSC70) play an important chaperoning role in unstressed cells, whereas the expression of the inducible (HSP70) forms is known to be activated by acute stressor insults (Morimoto et al, 1990) and pathological and environmental factors (Kiang and Tsokos, 1998), including psychological stress (Fukudo et al, 1997). HSPs, especially HSP70, can interact with denatured or misfolded proteins and assist in their recovery from stressful events, either by repairing (protein refolding) or degrading them (Ciocca et al, 1993;Hartman and Gething, 1996;Voellmy, 1996).A significant decrease in the levels of HSP70, one of the most important HSPs, was reported in the liver of acutely stressed male rats, whereas only a weak decrease in the levels of HSP70 was demonstrated in chronic stress models (Filipović et al, 2008). Moreover, the overexpression of HSP70 in the stomach of male rats seemed to protect against gastric ulcers, through its cytoprotective effects on the gastric mucosa, by increasing mucosal blood flow (Shichijo et al, 2003).…”

Molecular mechanisms of regulation of antioxidant enzymes in the brain and liver of acutely and/or chronically stressed rats

“…Decreased CORT levels in response to an additional IM or C stress in chronically-isolated animals compared to acute stressors alone indicates a compromised HPA axis activity resulting from prior chronic IS stress that could not recover after subsequent acute stressors. (Filipovic´et al, 2005). With the combined stressors, NO overproduction together with mitochondrial translocation of p53 in the PFC was observed.…”

“…In the current study, CORT levels were higher in the IM group than in the C group, confirming that IM was stress of high intensity (Garcia et al, 2000). Increased CORT levels following both acute stressors, act on prefrontal and hippocampal glucocorticoid receptors to reduce circulating levels of CORT (Filipovic´et al, 2005). Moreover, stress and glucocorticoids have been found to increase glutamate concentrations in the hippocampal synapse , resulting in the production of NO, which possesses both neuroprotective and neurodestructive properties (Dawson et al, 1991;Dawson and Dawson, 1995;McCaslin and Oh, 1995).…”

“…Moreover, NOdependent signaling pathways that initiate cell death may also involve the tumor suppressor protein p53 (Nakaya et al, 2000;Hofseth et al, 2003). This tumor suppressor protein can induce apoptosis independent of its transcriptional activity by rapid translocation from the cytoplasm to the mitochondria , causing changes in mitochondrial permeability that result in the release of apoptotic protein cytochrome c, the activation of caspase 3 , and eventually apoptosis Previous data from our laboratory have shown that 21 days of chronic isolation stress, an animal model of depression , compromises HPA axis activity by deregulating glucocorticoid negative feedback control in the central nervous system (CNS), especially in the hippocampus (HIPP) and cortex, due to impaired cytoplasmic/nuclear GR shuttling Filipovic´et al, 2005). Furthermore, we have recently demonstrated that chronic isolation stress-induced apoptosis in the rat prefrontal cortex (PFC) was accompanied by the release of cytochrome c and the activation of caspases-3 (Filipovic´et al, 2011).…”