Impact of the selective estrogen receptor modulator, tamoxifen, on neuronal outgrowth and survival following toxic insults associated with aging and Alzheimer's disease

Experimental Neurology
Kathleen O'NeillRoberta Diaz Brinton

Abstract

We investigated the estrogen agonist/antagonist properties of the selective estrogen receptor modulators (SERMs), tamoxifen (TMX) and 4-hydroxy-tamoxifen (OHT), using an in vitro neuron model system to determine the impact of the neuroprotective and neurotrophic properties of these SERMs. Low concentrations of TMX or OHT were without effect on a marker of neuronal viability, basal release of lactate dehydrogenase (LDH), whereas high concentrations of both SERMs (2500 ng/ml) induced a significant increase in LDH, indicating the potential toxicity of both SERMs at high concentrations. Subsequent experiments revealed that subtoxic concentrations of both TMX and OHT induced significant neuroprotection against beta-amyloid(25-35)-induced toxicity; 15-20% and 10-15% (P < 0.05), respectively and also against glutamate-induced toxicity; 25-30% and 20-40% (P < 0.05 and P < 0.01), respectively. Additional in vitro experiments included analysis of neuron survival to determine whether the SERM, OHT, acted competitively or synergistically with the endogenous estrogen, 17 beta-estradiol (E2). These revealed that neuron survival following exposure to the neurotoxins beta-amyloid and excitotoxic glutamate was significantly increased in culture...Continue Reading

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