Glucocorticoid receptor changes are associated with age in the hippocampus of Zucker diabetic fatty rats

Abstract

Diabetes is a metabolic disorder that is associated with dysfunction of a number of systems within the body and an excess of glucocorticoid is one of the characteristics seen in patients with type 2 diabetes. In the present study, we investigated the glucocorticoid receptor (GR) immunoreactivity and its protein levels in the hippocampus of 4-(pre-diabetic), 12-, 20- and 30-week-old Zucker diabetic fatty (fa/fa, ZDF) rats and Zucker lean control (fa/+, +/+, ZLC) rats. Progressive diabetic condition gradually develops from 7 weeks of age and is complete at 12 weeks of age in ZDF rats, thereafter the chronic diabetic condition is maintained. GR immunoreactivity was mainly detected in the hippocampal CA1 and dentate gyrus, and GR protein levels were exponentially increased along with the age. The GR immunoreactivity and protein levels were markedly increased in ZDF rats than in age-matched ZLC rats except in the 4-weekold group. GR protein levels in the hippocampus of the 20- and 30-week ZDF rats were significantly increased compared with the 4- and 12-week-old ZDF rats. The present study suggests that GR immunoreactivity and its protein level in type 2 diabetic conditions are associated with age, and the GR expression in the hippocampus may be significantly increased in progressive chronic type 2 diabetic condition.