Journal
BRAIN RESEARCH
Volume 998, Issue 1, Pages 65-72Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2003.11.012
Keywords
Pb2+; ERK1/2; p38(MAPK); hippocampus; brain slice; protein phosphorylation
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Lead (Pb2+) is widely recognized as a neurotoxicant whose mechanisms of action are not completely established. We have previously demonstrated that Pb2+ can activate the p38(MAPK) pathway and increase the phosphorylation of Hsp27 in bovine adrenal chromaffin 6 ells and human SH SY5Y cells over a short incubation period (I h). In the present work we analyzed the effects of Pb2+ administered in vivo on the level and the phosphorylation state of ERK1/2 and p38(MAPK) in the hippocampus of immature rats. Rats were treated with lead acetate (2, 8 or 12 mg/kg, i.p.) or saline (control) over the 8th to 12th postnatal days, and hippocampal slices were prepared on the 14th day. The Pb2+ level in the lead-treated animals increased 2.5-6-fold in the blood (3.0-6.0 mug/dl) and 2.0-3.0-fold in the forebrain (78-103 ng/g wet weight), compared to control (saline). The phosphorylation of both ERK1/2 and p38(MAPK) was significantly increased by prior exposure to Pb2+ in vivo. In in vitro experiments, hippocampal slices from 14-day-old rats were exposed to Pb2+ (1-10 muM) for 1 and 3 h. There were no changes in the phosphorylation state of ERK and p38(MAPK) for 1-h incubation, whereas a significant increase of ERK1/2 and p38(MAPK) phosphorylation by Pb2+ (5 muM) was observed for the 3-h incubation. Cell viability measured using MTT was not modified in any of the conditions tested. These results indicate that the phosphorylation of hippocampal ERK1/2 and p38(MAPK) is stimulated by lead in a period of rapid brain development, an effect that may underlie, at least in part, the neurotoxicty elicited by this metal. (C) 2003 Elsevier B.V. All rights reserved.
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