title: Regulation of glutamate transporter GLAST and GLT-1 expression in astrocytes by estrogen.
abstract: Estrogen influences neuronal development and a broad spectrum of neural functions. In addition, several lines of evidence suggest a role as neuroprotective factor for estrogen in the CNS. Neuroprotection can result from direct estrogen-neuron interactions or be mediated indirectly involving the regulation of physiological properties of nonneuronal cells, such as astrocytes and microglia. Increased l-glutamate levels are associated with neurotoxic and neurodegenerative processes in the brain. Thus, the removal of l-glutamate from the extracellular space by astrocytes through the astroglial glutamate transporters GLT-1 and GLAST appears essential for maintaining a homeostatic milieu for neighboring neurons. We have therefore studied the influence of 17beta-estradiol on l-glutamate metabolism in cultured astrocytes from the neonate mouse midbrain using quantitative RT-PCR and Western blotting for both transporters as well as functional l-glutamate uptake studies. The administration of estrogen significantly increased the expression of GLT-1 and GLAST on the mRNA and protein level. Likewise, specific l-glutamate uptake by astrocytes was elevated after estrogen exposure and mimicked by dbcAMP stimulation. Induction of transporter expression and l-glutamate uptake were sensitive to ICI 182,780 treatment suggesting estrogen action through nuclear estrogen receptors. These findings indicate that estrogen can prevent l-glutamate-related cell death by decreasing extracellular l-glutamate levels through an increased l-glutamate uptake capacity by astrocytes.
authors.affiliation: Anatomisches Institut, Universität Tübingen, Osterbergstr. 3, 72074 Tübingen, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Pawlak
authors.forename: Veronica
authors.initials: V
authors.lastname: Brito
authors.forename: Eva
authors.initials: E
authors.lastname: Küppers
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D027322:Amino Acid Transport System X-AG; D004965:Estrogen Antagonists; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; C493393:Slc1a3 protein, mouse; D027981:Symporters; D000077267:Fulvestrant; D018698:Glutamic Acid; D004958:Estradiol; D003994:Bucladesine