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

Objectives: The current study investigated the neurotrophic and neuroprotec tive action of the complex formulation of conjugated equine estrogens (CEEs ), the most frequently prescribed estrogen replacement therapy in the Unite d States and the estrogen replacement therapy of the Women's Health Initiat ive. Methods: Videomicroscopic, morphologic and biochemical analyses were c onducted in primary cultures of hippocampal neurons to determine the neurot rophic and neuroprotective properties of CEEs. Results: Results of these an alyses demonstrated that CEEs significantly increased hippocampal neuronal outgrowth, a cellular marker of memory formation. Dose response analyses in dicated that the lowest effective concentration of CEEs exerted the maximal neurotrophic effect. Results of neuroprotection studies demonstrated that GEES induced highly significant neuroprotection against beta amyloid(25-35) , hydrogen peroxide and glutamate-induced toxicity. Conclusions: CEEs induc ed cellular markers of memory function in neurons critical to memory and vu lnerable to negative effects of aging and Alzheimer's disease. In addition, CEEs significantly and potently protected neurons against toxic insults as sociated with Alzheimer's disease. Because CEEs are the estrogen replacemen t therapy of the Women's Health Initiative, results of the current study co uld provide cellular mechanisms for effects of CEEs on cognitive function a nd risk of Alzheimer's disease derived from this prospective clinical trial . (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.