THE ROLE OF GLUCOCORTICOIDS IN BRAIN AGING AND ALZHEIMERS-DISEASE - AN INTEGRATIVE PHYSIOLOGICAL HYPOTHESIS

The glucocorticoid hypothesis of brain aging, which proposes that expo sure of brain cells to glucocorticoids can increase brain cell loss du ring aging, is a physiological aging hypothesis that emphasizes intera ctions among systems. Thus, it fits well with the concepts advanced by Nathan Shock. The historical background of the hypothesis, the hypoth esis and supporting data, and several modifications are briefly review ed here, as are recent mechanistic studies linking hippocampal glucoco rticoid receptor activation to increased voltage-activated calcium inf lux. These new data suggest that some aspects of the impact of glucoco rticoids on brain cells may increase rather than decrease with aging, and that some of the etiology of aging-related neurotoxicity may depen d on gradually accumulating endocrine dysregulation of neuronal calciu m homeostasis.