Different trends in modulation of NMDAR1 and NMDAR2B gene expression in cultured cortical and hippocampal neurons after lead exposure

W. K. Lau, C. W. Yeung, P. W. Lui, L. H. Cheung, N. T. Poon, Kin Lam YUNG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10-24
Number of pages15
JournalBrain Research
Volume932
Issue number1-2
DOIs
Publication statusPublished - 5 Apr 2002

Scopus Subject Areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

User-Defined Keywords

  • Heavy metal toxicity
  • Ionotropic glutamate receptor
  • Learning and memory
  • Rat

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