PMID- 12750004
OWN - NLM
STAT- MEDLINE
DCOM- 20030818
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 113
IP  - 1-2
DP  - 2003 May 12
TI  - Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of 
      Pb2+-exposed rats: implications for synaptic targeting and cell surface 
      expression of NMDAR complexes.
PG  - 37-43
AB  - We have previously shown that exposure to environmentally relevant levels of 
      Pb(2+) during brain development decreases the expression of N-methyl-D-aspartate 
      receptor (NMDAR) subunit 1 (NR1) and NR2A genes in the hippocampus of young adult 
      rats and was associated with deficits in hippocampal LTP and spatial learning 
      [Neuroscience 99 (2000) 233-242]. In the present study, we demonstrate that the 
      lower levels of NR1 subunit mRNA expressed in the Pb(2+)-exposed hippocampus are 
      principally due to decreased levels of the NR1-4 and NR1-2 splice variants. These 
      changes were present in the absence of changes in GluR1, PSD-95 and alphaCaMKII 
      gene expression. A unique characteristic of these splice variants is that they 
      lack the C1 cassette. Further, these splice variants have been shown to impart 
      the highest cell surface expression, PKC potentiation and calcium kinetics to 
      NMDAR complexes. Our present findings indicate that Pb(2+)-induced changes in NR1 
      subunit splice variant mRNA expression in the hippocampus may provide a mechanism 
      by which Pb(2+)-exposure can modify NMDAR-mediated calcium signaling and 
      influence the degree of synaptic plasticity.
FAU - Guilarte, Tomas R
AU  - Guilarte TR
AD  - Molecular Neurotoxicology Laboratory, Department of Environmental Health 
      Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, 
      MD 21205, USA. tguilart@jhsph.edu
FAU - McGlothan, Jennifer L
AU  - McGlothan JL
LA  - eng
GR  - ES06189/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 (NR1 NMDA receptor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 2P299V784P (Lead)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Alternative Splicing/drug effects/genetics
MH  - Animals
MH  - Down-Regulation/*drug effects/genetics
MH  - Environmental Exposure
MH  - Female
MH  - Hippocampus/*drug effects/metabolism/pathology
MH  - Lead/*toxicity
MH  - Lead Poisoning, Nervous System/*genetics/*metabolism/physiopathology
MH  - Male
MH  - Neuronal Plasticity/drug effects/genetics
MH  - Presynaptic Terminals/*drug effects/metabolism
MH  - Protein Isoforms/genetics
MH  - Protein Kinase C/drug effects/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, Cell Surface/genetics
MH  - Receptors, N-Methyl-D-Aspartate/*genetics
MH  - Synaptic Transmission/drug effects/genetics
EDAT- 2003/05/17 05:00
MHDA- 2003/08/19 05:00
CRDT- 2003/05/17 05:00
PHST- 2003/05/17 05:00 [pubmed]
PHST- 2003/08/19 05:00 [medline]
PHST- 2003/05/17 05:00 [entrez]
AID - S0169328X03000834 [pii]
AID - 10.1016/s0169-328x(03)00083-4 [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 2003 May 12;113(1-2):37-43. doi: 
      10.1016/s0169-328x(03)00083-4.