title: Aroclor 1254 selectively inhibits expression of glial GLT-1 glutamate transporter in the forebrain of chronically exposed adult rat.
abstract: Aroclor 1254, a commercially produced mixture of polychlorinated biphenyls, is known to cause many adverse conditions, including neurotoxicity. It has been recently postulated that upregulation of N-methyl-d-aspartate receptors (NMDARs) and enhanced glutamate signalling which leads to excitotoxicity, is the mechanism of Aroclor-induced neurotoxicity. To obtain insights into the mechanisms underlying glutamatergic overstimulation, we investigated the function and expression of sodium-dependent glutamate transporters which are known to regulate extracellular glutamate concentrations in the brain. Exposure to Aroclor 1254 was found to significantly lower the uptake of radioactive glutamate into gliosomal fractions obtained from adult rat brains. It also markedly decreased the expression of both protein and mRNA of GLT-1, the main glial glutamate transporter. This indicates that downregulation of GLT-1 may potentially lead to disturbances in glutamate clearance. The expression of GLAST, another astroglial glutamate transporter, was unchanged under conditions of Aroclor toxicity. Conversely, we observed enhanced glutamate uptake into nerve-endings fractions paralleled by increased EAAC1 protein expression. This may reflect the induction of protective mechanisms.
authors.affiliation: Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str., 02-106 Warsaw, Poland. lidkas@cmdik.pan.pl
authors.forename: Lidia
authors.initials: L
authors.lastname: Strużyńska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sulkowski
authors.forename: Beata
authors.initials: B
authors.lastname: Dąbrowska-Bouta
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000009:adverse effects*; D027341:Excitatory Amino Acid Transporter 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects*; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D020111:Chlorodiphenyl (54% Chlorine)