Decreased levels of nuclear glucocorticoid receptor protein in the hippocampus of aged Long-Evans rats with cognitive impairment

Abstract

Previous studies using animal models of cognitive aging showed that hypothalamic-pituitary-adrenal (HPA) responses to stress are impaired and glucocorticoid receptor (GR) mRNA is decreased in cognitively impaired aged rats, compared with those in young rats and cognitively unimpaired aged rats. Increased HPA activity is associated with the loss of hippocampal corticosteroid receptors. In the current investigation, GR expressions in the hippocampus were examined in young and aged male Long-Evans rats whose spatial memory was initially assessed on the Morris water maze task. We evaluated GR protein level in the hippocampus in young and aged rats characterized on the basis of the spatial task. In the hippocampus of aged rats with spatial memory impairments, GR protein level was decreased in the nucleus but not in the cytosol, and levels of glucocorticoid response elements binding activity was decreased. These results suggest that GR signaling is impaired in the hippocampus of rats with cognitive impairment. Impaired GR signaling may contribute to HPA axis dysfunction in aged rats and aged humans with cognitive impairment.