17β-Estradiol attenuates oxidative impairment of synaptic Na+/K+-ATPase activity, glucose transport, and glutamate transport induced by amyloid β-peptide and iron

• Published in: Journal of neuroscience research Vol. 50; no. 4; pp. 522 - 530
• Main Authors: Keller, Jeffrey N., Germeyer, Ariane, Begley, James G., Mattson, Mark P.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15.11.1997
• Subjects: Alzheimer's disease; estrogen; free radicals; glucocorticoids; hydroxynonenal; lipid peroxidation; mitochondrial electron transport; neuronal death; progesterone; thiobarbituric acid
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(19971115)50:4<522::AID-JNR3>3.0.CO;2-G

Synapse loss, deposits of amyloid β‐peptide (Aβ), impaired energy metabolism, and cognitive deficits are defining features of Alzheimer's disease (AD). Estrogen replacement therapy reduces the risk of developing AD in postmenopausal women. Because synapses are likely sites for initiation of neurodegenerative cascades in AD, we tested the hypothesis that estrogens act directly on synapses to suppress oxidative impairment of membrane transport systems. Exposure of rat cortical synaptosomes to Aβ25‐35 (Aβ) and FeSO4 induced membrane lipid peroxidation and impaired the function of the plasma membrane Na+/K+‐ATPase, glutamate transporter, and glucose transporter. Pretreatment of synaptosomes with 17β‐estradiol or estriol largely prevented impairment of Na+/K+‐ATPase activity, glutamate transport, and glucose transport; other steroids were relatively ineffective. 17β‐Estradiol suppressed membrane lipid peroxidation induced by Aβ and FeSO4, but did not prevent impairment of membrane transport systems by 4‐hydroxynonenal (a toxic lipid peroxidation product), suggesting that an antioxidant property of 17β‐estradiol was responsible for its protective effects. By suppressing membrane lipid peroxidation in synaptic membranes, estrogens may prevent impairment of transport systems that maintain ion homeostasis and energy metabolism, and thereby forestall excitotoxic synaptic degeneration and neuronal loss in disorders such as AD and ischemic stroke. J. Neurosci. Res. 50:522–530, 1997. © 1997 Wiley‐Liss, Inc.