Neuroprotective role of estrogen in oxidative stress induced neurodegeneration: implications for neurotoxic insult.
Toxicologist 1999 Mar; 48(1-S):415
Certain neurodegenerative diseases like Parkinson's disease, affect more men than women and women with Alzheimer's disease receiving hormone replacement therapy show a lessened severity and slowed disease progression. Estrogen may have antioxidant properties as these diseases are linked to oxidative damage. In vitro studies utilizing neural tissue have own that 17Beta-estradiol can decrease excitotoxic damage by directly inhibiting the NMDA receptor and limit the damage caused by Beta-amyloid peptides, a suspected etiological agent in Alzheimer's disease. In examining the striatal dopaminergic neurotoxicity of agents such as MPTP and methamphetamine (METH) that are suspected to cause neuronal injury by oxidative stress, greater dopaminergic neurotoxicity was noted in males. Evidence linking estrogen to this gender difference was provided by the finding that ovariectomized (OVX) mice, compared to mice receiving 17Beta-estradiol, displayed greater striatal damage in response to MPTP suggesting that estrogen has neuroprotective properties in this model of striatal dopaminergic neurotoxicity. Protection was not linked to alterations in metabolism or generation of the proximal toxicant although estrogen is known to affect metabolic processes. Similar neuroprotective effects of estrogen were found for METH-induced dopaminergic neurotoxicity and others have reported greater striatal damage in OVX female rats receiving 6-hydroxydopamine, another dopaminergic neurotoxicant suspected to damage tissue through a free radical/oxidative stress mechanism. Whether other estrogenic compounds, including tamoxiten, the triphenylethylenes, and the phytoestrogens, can mimic or disrupt the neuroprotective actions of estrogen has received limited examination or discussion.
Toxins; Toxicology; Toxic-materials; Hormones; Hormone-activity; Estrogenic-hormones; Neurotoxins; Neurotoxic-effects; Biological-function; Animal-studies; Laboratory-animals
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana