PMID- 10095076 OWN - NLM STAT- MEDLINE DCOM- 19990513 LR - 20190826 IS - 0169-328X (Print) IS - 0169-328X (Linking) VI - 66 IP - 1-2 DP - 1999 Mar 20 TI - NMDAR-2A subunit protein expression is reduced in the hippocampus of rats exposed to Pb2+ during development. PG - 42-9 AB - Chronic exposure to lead (Pb2+) produces deficits of learning and memory in children and spatial learning deficits in developing rats. The N-methyl-D-aspartate receptor (NMDAR) has been identified as a principal target for Pb2+-induced neurotoxicity. Age-dependent changes in NMDAR subunit gene expression were observed in hippocampi of rats chronically exposed to Pb2+ during development [T.R. Guilarte, J.L. McGlothan, Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure, Brain Res. 790 (1998) 98-107]. These changes were present at blood Pb2+ levels ranging from 20-60 microg/dl. Littermates were used in the present study to determine whether the changes in gene expression were reflected in protein levels. NR1, NR2A, and NR2B subunit protein levels were measured in rat hippocampus and cortex at post-natal days (PND) 7, 14, 21, and 28 by Western blot and densitometric analysis. A treatment effect was apparent for NR2A subunit protein expression in the hippocampus (F1,28=10.224, p<0.01). NR2A subunit protein was reduced by 40%, 19%, and 27% from control levels in PND14, 21, and 28 Pb2+-exposed rats, respectively. Mean comparisons indicated that rats at PND14 exhibited the most significant reduction of NR2A (p<0.001). These data concur with our previous finding of reduced NR2A mRNA found in hippocampal pyramidal and granule cells of Pb2+-exposed rats. Pb2+ exposure during development had no effect on NR1 or NR2B subunit protein expression in the hippocampus at any age. No effect was observed on any subunit in the cortex at any age. The developmental profile of the NMDAR-2A subunit protein in the hippocampus is specifically changed by chronic exposure to Pb2+. These data suggest that composition of subunits comprising NMDAR may be altered in Pb2+-exposed rats. CI - Copyright 1999 Elsevier Science B.V. FAU - Nihei, M K AU - Nihei MK AD - Department of Environmental Health Sciences, The Johns Hopkins University, Room 2001, School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD, USA. FAU - Guilarte, T R AU - Guilarte TR LA - eng GR - ES03819/ES/NIEHS NIH HHS/United States GR - ES06189/ES/NIEHS NIH HHS/United States GR - T32 ES07141/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res Mol Brain Res JT - Brain research. Molecular brain research JID - 8908640 RN - 0 (Organometallic Compounds) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 2P299V784P (Lead) RN - RX077P88RY (lead acetate) SB - IM MH - Age Factors MH - Animals MH - Blotting, Western MH - Brain Chemistry/drug effects MH - Female MH - Hippocampus/cytology/*drug effects/*growth & development MH - Lead/analysis/blood/pharmacology MH - Neurons/chemistry/drug effects/*metabolism MH - Organometallic Compounds/analysis/blood/*pharmacology MH - Rats MH - Rats, Long-Evans MH - Receptors, N-Methyl-D-Aspartate/analysis/*biosynthesis EDAT- 1999/03/30 00:00 MHDA- 1999/03/30 00:01 CRDT- 1999/03/30 00:00 PHST- 1999/03/30 00:00 [pubmed] PHST- 1999/03/30 00:01 [medline] PHST- 1999/03/30 00:00 [entrez] AID - S0169-328X(99)00005-4 [pii] AID - 10.1016/s0169-328x(99)00005-4 [doi] PST - ppublish SO - Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):42-9. doi: 10.1016/s0169-328x(99)00005-4.