Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer's disease patients.
Estrogen is thought to play a protective role against neurodegeneration through a variety of mechanisms including the activation of growth factors, the control of synaptic plasticity, and the reduction of response to various insults, such as iron and glutamate. Increasing evidence indicates an increased level of extracellular glutamate and a down-regulation of glutamate transporters in Alzheimer's disease (AD). In this study, we show that glutamate uptake in astrocytes derived from Alzheimer's patients is significantly lower than that from non-demented controls. Estrogen treatment increases glutamate uptake in a dose-dependent pattern. Two glutamate transporters, GLT-1 and GLAST, are expressed in the astrocytes. Up-regulation of the glutamate transporters is induced by estrogen treatment in AD astrocytes only. Our data suggest that the action of estrogen on glutamate uptake by astrocytes might contribute to its potential neuroprotective role in AD.
Liang
Zhe
Z
Roberts Alzheimer's Research Center, Sun Health Research Institute, Sun City, Arizona, USA.
Valla
Jon
J
Sefidvash-Hockley
Sepideh
S
Rogers
Joseph
J
Li
Rena
R
D000544:Alzheimer Disease / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D006801:Humans; D007150:Immunohistochemistry
D027322:Amino Acid Transport System X-AG; D004967:Estrogens; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; D004958:Estradiol