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Differential expression of N ‐methyl‐ d ‐aspartate receptor NR2 isoforms in Alzheimer's disease
Author(s) -
Hynd Matthew R.,
Scott Heather L.,
Dodd Peter R.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02548.x
Subject(s) - gene isoform , nmda receptor , excitotoxicity , protein subunit , western blot , receptor , biology , microbiology and biotechnology , messenger rna , alternative splicing , gene , biochemistry
We have previously shown that the expression of NMDA receptor NR1 subunit mRNA splice variants in Alzheimer's disease (AD) brain varies according to regional susceptibility to pathological damage. Here we investigated the expression of the modulatory NR2 subunits of the NMDA receptor using quantitative RT–PCR to assay all NR2 isoforms. Significantly lower expression of NR2A and NR2B transcripts was found in susceptible regions of AD brain, whereas expression of NR2C and NR2D transcripts did not differ from that in controls. Western blot analysis confirmed a lower expression of the NR2A and NR2B isoforms at the protein level. The results suggest that NR2 subunit composition may modulate NMDA receptor‐mediated excitotoxicity. NMDA receptor dysfunction might give rise to the regionally selective pattern of neuronal loss that is characteristic of AD.