The role of astroglia in Pb-exposed adult rat brain with respect to glutamate toxicity.
Astrocytes maintain neuronal homeostasis in brain and controlling of the released glutamate is one of the most important functions. Since it is suggested that glutamatergic component underlies lead-induced neurotoxic effects and simultaneously, astrocytes serve as a cellular lead (Pb) deposition site, it was of interest to investigate the functioning of astroglia in adult rat brain after short-term exposure to Pb. We examined the expression of main astrocytic glutamate/aspartate transporters--GLAST and GLT-1, which regulate extracellular glutamate concentration. Molecular evidence is provided which indicates overexpression of GLAST mRNA and protein. Simultaneously, decreased expression of GLT-1 mRNA and protein was observed, indicating that of the two glial transporters, GLT-1 is more susceptible to the toxic Pb effect. Protein expression of glutamine synthetase (GS), which converts toxic glutamate to non-toxic glutamine, was doubly enhanced. Moreover, Na+-dependent transport of radioactive glutamine to astroglia-derived fraction was affected in Pb-exposed rats. Both the rate of accumulation and the efflux of amino acid were diminished. Additionally, we observed enhanced expression of glutathione-protein complexes after Pb treatment what suggests activation of S-glutathionylation processes. The results of current studies indicate that lead toxicity in adult rat brain activates astrocytic processes connected with the controlling of glutamate homeostasis. The response of astroglia is rather of neuroprotective character however, downexpression of GLT-1 glutamate transporter and activation of S-glutathionylation processes lead to the question about their significance in Pb-induced neurotoxicity.
Struzyńska
Lidia
L
Laboratory of Pathoneurochemistry, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str., 02-106 Warsaw, Poland. lidkas@cmdik.pan.pl
Chalimoniuk
Małgorzata
M
Sulkowski
Grzegorz
G
D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007854:Lead / Q000032:analysis / Q000633:toxicity*; D008297:Male; D016548:Prosencephalon / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D005973:Glutamine; D007854:Lead; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione