The estrogen replacement therapy of the Women's Health Initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to Alzheimer's disease

Objectives: The current study investigated the neurotrophic and neuroprotective action of the complex formulation of conjugated equine estrogens (CEEs), the most frequently prescribed estrogen replacement therapy in the United States and the estrogen replacement therapy of the Women's Health Initiative. Methods: Videomicroscopic, morphologic and biochemical analyses were conducted in primary cultures of hippocampal neurons to determine the neurotrophic and neuroprotective properties of CEEs. Results: Results of these analyses demonstrated that CEEs significantly increased hippocampal neuronal outgrowth, a cellular marker of memory formation. Dose response analyses indicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect. Results of neuroprotection studies demonstrated that CEES induced highly significant neuroprotection against beta amyloid_25-35, hydrogen peroxide and glutamate-induced toxicity. Conclusions: CEEs induced cellular markers of memory function in neurons critical to memory and vulnerable to negative effects of aging and Alzheimer's disease. In addition, CEEs significantly and potently protected neurons against toxic insults associated with Alzheimer's disease. Because CEEs are the estrogen replacement therapy of the Women's Health Initiative, results of the current study could provide cellular mechanisms for effects of CEEs on cognitive function and risk of Alzheimer's disease derived from this prospective clinical trial. Copyright (C) 2000 Elsevier Science Ireland Ltd.