Brinton Roberta Diaz. Chen Shuhu. Montoya Mariss. Hsieh Debr. Minaya
Jasmin.
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, Maturitas 34(Suppl. 2) :S35-S52, 2000.
Abstract
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 amyloid25-35, 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.
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