J Vet Sci.  2014 Mar;15(1):19-26. 10.4142/jvs.2014.15.1.19.

Sequential alterations of glucocorticoid receptors in the hippocampus of STZ-treated type 1 diabetic rats

• Shin JH
• Seong JK
• Yi SS

• KMID: 1737606
• DOI: http://doi.org/10.4142/jvs.2014.15.1.19

Abstract

Type 1 diabetes is a common metabolic disorder accompanied by increased blood glucose levels along with glucocorticoid and cognitive deficits. The disease is also thought to be associated with environmental changes in brain and constantly induces oxidative stress in patients. Therefore, glucocorticoid-mediated negative feedback mechanisms involving the glucocorticoid receptor (GR) binding site are very important to understand the development of this disease. Many researchers have used streptozotocin (STZ)-treated diabetic animals to study changes in GR expression in the brain. However, few scientists have evaluated the hyperglycemic period following STZ exposure. In the present study, we found GR expression in the hippocampus varied based on the period after STZ administration for up to 4 weeks. We performed immunohistochemistry and Western blotting to validate the sequential alterations of GR expression in the hippocampus of STZ-treated type 1 diabetic rats. GR protein expression increased significantly until week 3 but decreased at week 4 following STZ administration. GR expression after 70 mg/kg STZ administration was highest at 3 weeks post-treatment and decreased thereafter. Although STZ-induced increase in GR expression in diabetic animals has been described, our data indicate that researchers should consider the sequential GR expression changes during the hyperglycemic period following STZ exposure.

Keyword

glucocorticoid receptor; hippocampus; hyperglycemic period; streptozotocin; type 1 diabetes

MeSH Terms

Animals
Diabetes Mellitus, Experimental/chemically induced/*metabolism/*physiopathology
Disease Models, Animal
*Gene Expression Regulation
Hippocampus/metabolism/*physiopathology
Humans
Male
Rats
Rats, Wistar
Receptors, Glucocorticoid/*genetics/*metabolism
Time Factors
Receptors, Glucocorticoid

Figure

• 

  Fig. 1 Physiological data for the control and STZ-treated rats. Body weights of the vehicle group exponentially increased while those of the STZ-treated rats slowly decreased over the 4-week study period (A). Blood glucose levels at baseline and 1, 2, 3, and 4 weeks post-STZ treatment were significantly different from those of the control. Blood glucose levels continuously increased in STZ-treated animals from 385 mg/dL at 1 week (B). Food intake and water consumption also noticeably increased from 1 week post-STZ treatment (C and D; *p < 0.005). Results are expressed as the mean ± SE.

• 

  Fig. 2 Plasma corticosterone levels in STZ-treated rats. Plasma corticosterone levels at 2-, 3-, and 4-weeks post-STZ treatment (STZ2w, STZ3w, and STZ4w, respectively) were significantly different from those of the control (n = 5 per group, *p < 0.001 and **p < 0.05). Plasma corticosterone levels were reduced in the STZ3w group; however, the levels were significantly high than that of the control. Results are expressed as the mean ± SE.

• 

  Fig. 3 Immunoreactivities specific for the glucocorticoid receptor (GR) in the hippocampus (CA1 and dentate gyrus; DG) of control and STZ-treated rats at 2, 3, and 4 weeks after STZ administration. GR-immunopositive cell counts (E) and relative optical densities (ROD) expressed as % values of GR (F) relative to that of the control animals in the CA1 and DG are presented in the bar graphs. The fields showing GR-specific immunostained cells in the CA1 (C1) and DG (C2) are magnified. The GR-immunopositive cell counts for the CA1 of each group were not significantly different. However, those in the DG from STZ3w to STZ4w were significantly higher compared to the numbers found in the control (E; *p < 0.05). The intensities of GR-specific immunostained cells were significantly increased from STZ3w to STZ4w in the CA1 and DG regions compared to the control (F; *p < 0.05 and **p < 0.001). Results are expressed as the mean ± SE. Scale bars = 100 µm.

• 

  Fig. 4 Western blot analysis of GR expression in the hippocampus region of the control and STZ-treated rats 2, 3, and 4 weeks (STZ2w, STZ3w and STZ4w, respectively) after STZ exposure. ROD values are expressed as percentages versus GR protein levels observed in the control (n = 5 per group). The values were normalized to those of GAPDH. Results are expressed as the mean ± SE.

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