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

Jeffrey N. Keller, Ariane Germeyer, James G. Begley, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)522-530
Number of pages9
JournalJournal of Neuroscience Research
Volume50
Issue number4
DOIs
StatePublished - Nov 15 1997
Externally publishedYes

Fingerprint

Amyloid
Lipid Peroxidation
Glutamic Acid
Estradiol
Alzheimer Disease
Membrane Lipids
Iron
Synapses
Glucose
Peptides
Synaptosomes
Energy Metabolism
Estrogens
Amino Acid Transport System X-AG
Synaptic Membranes
Estriol
Estrogen Replacement Therapy
Membranes
Facilitative Glucose Transport Proteins
Poisons

Keywords

  • Alzheimer's disease
  • Estrogen
  • Free radicals
  • Glucocorticoids
  • Hydroxynonenal
  • Lipid peroxidation
  • Mitochondrial electron transport
  • Neuronal death
  • Progesterone
  • Thiobarbituric acid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

17β-Estradiol attenuates oxidative impairment of synaptic Na+/K+- ATPase activity, glucose transport, and glutamate transport induced by amyloid β-peptide and iron. / Keller, Jeffrey N.; Germeyer, Ariane; Begley, James G.; Mattson, Mark P.

In: Journal of Neuroscience Research, Vol. 50, No. 4, 15.11.1997, p. 522-530.

Research output: Contribution to journalArticle

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