TY - JOUR
T1 - Different trends in modulation of NMDAR1 and NMDAR2B gene expression in cultured cortical and hippocampal neurons after lead exposure
AU - Lau, W. K.
AU - Yeung, C. W.
AU - Lui, P. W.
AU - Cheung, L. H.
AU - Poon, N. T.
AU - Yung, Kin Lam
N1 - Funding Information:
The present work was supported by FRG/98-99/II-31, Faculty Research Grant, Hong Kong Baptist University. WKL was supported by HKBU2053/00M, Research Grant Council, Hong Kong. PWL was supported by a postgraduate studentship, Hong Kong Baptist University. CWY was supported by HKBU2/00C Central allocation, Research Grant Council, Hong Kong. The authors would like to thank Miss L.Y. Man for technical assistance.
PY - 2002/4/5
Y1 - 2002/4/5
N2 - Exposure to heavy metal lead (Pb2+) has been reported to cause problems in cognitive functions of the brain, e.g. memory loss and difficulties in mental development. N-Methyl-D-aspartate receptors (NRs) are important molecules that are known to be involved in mediation of learning and memory. In order to investigate the effects of Pb2+ on the gene expression of NR1 and NR2B subunits in neurons, primary cell cultures of rat cortical and hippocampal neurons were employed. After treatments with different concentrations of Pb2+ ions in culture medium (0, 5, 10, 25 and 50 μM), the cellular localization of Pb2+ in neurons was evaluated by laser scan confocal microscopy by using a Pb2+ ion specific fluorescence probe. In addition, the gene expression of NR1 and NR2B subunits was determined by reverse transcriptase-polymerase chain reaction, immunofluorescence and Western blotting. The results of the present study showed that both cortical and hippocampal neurons accumulated intracellular Pb2+ in accordance with the concentrations of Pb2+ ions present in the culture medium. After Pb2+ treatments, levels of NR1 mRNA, immunoreactivity and protein were found to be unchanged but levels of NR2B mRNA, immunoreactivity and protein were found to be significantly increased in cortical neurons. In contrast, both NR1 and NR2B mRNAs, immunoreactivity and proteins were found to be significantly decreased in hippocampal neurons. The changes in gene expression were found to be dose dependent in accordance with the Pb2+ concentrations. The present results indicate that Pb2+ has a differential effect on the expression of NR1 and NR2B subunits in cortical and hippocampal neurons, respectively. It is likely that the toxic effects of Pb2+ may cause differential damage to different types of memory that are mediated by cortical and hippocampal neurons, respectively.
AB - Exposure to heavy metal lead (Pb2+) has been reported to cause problems in cognitive functions of the brain, e.g. memory loss and difficulties in mental development. N-Methyl-D-aspartate receptors (NRs) are important molecules that are known to be involved in mediation of learning and memory. In order to investigate the effects of Pb2+ on the gene expression of NR1 and NR2B subunits in neurons, primary cell cultures of rat cortical and hippocampal neurons were employed. After treatments with different concentrations of Pb2+ ions in culture medium (0, 5, 10, 25 and 50 μM), the cellular localization of Pb2+ in neurons was evaluated by laser scan confocal microscopy by using a Pb2+ ion specific fluorescence probe. In addition, the gene expression of NR1 and NR2B subunits was determined by reverse transcriptase-polymerase chain reaction, immunofluorescence and Western blotting. The results of the present study showed that both cortical and hippocampal neurons accumulated intracellular Pb2+ in accordance with the concentrations of Pb2+ ions present in the culture medium. After Pb2+ treatments, levels of NR1 mRNA, immunoreactivity and protein were found to be unchanged but levels of NR2B mRNA, immunoreactivity and protein were found to be significantly increased in cortical neurons. In contrast, both NR1 and NR2B mRNAs, immunoreactivity and proteins were found to be significantly decreased in hippocampal neurons. The changes in gene expression were found to be dose dependent in accordance with the Pb2+ concentrations. The present results indicate that Pb2+ has a differential effect on the expression of NR1 and NR2B subunits in cortical and hippocampal neurons, respectively. It is likely that the toxic effects of Pb2+ may cause differential damage to different types of memory that are mediated by cortical and hippocampal neurons, respectively.
KW - Heavy metal toxicity
KW - Ionotropic glutamate receptor
KW - Learning and memory
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=0037023197&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(01)03395-9
DO - 10.1016/S0006-8993(01)03395-9
M3 - Journal article
C2 - 11911857
AN - SCOPUS:0037023197
SN - 0006-8993
VL - 932
SP - 10
EP - 24
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -