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Glutamate NMDA receptor NR1 subunit mRNA expression in Alzheimer's disease
Author(s) -
Hynd Matthew R.,
Scott Heather L.,
Dodd Peter R.
Publication year - 2001
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 - 10.1046/j.1471-4159.2001.00409.x
Subject(s) - biology , nmda receptor , cerebral cortex , cingulate cortex , microbiology and biotechnology , glutamate receptor , human brain , cortex (anatomy) , endocrinology , medicine , receptor , neuroscience , central nervous system , genetics
We analyzed the expression profile of two NMDAR1 mRNA isoform subsets, NR1 0XX and NR1 1XX , in discrete regions of human cerebral cortex. The subsets are characterized by the absence or presence of a 21‐amino acid N‐terminal cassette. Reverse transcription polymerase chain reaction for NR1 isoforms was performed on total RNA preparations from spared and susceptible regions from 10 pathologically confirmed Alzheimer's disease (AD) cases and 10 matched controls. Primers spanning the splice insert yielded two bands, 342 bp (NR1 0XX ) and 405 bp (NR1 1XX ), on agarose gel electrophoresis. The bands were visualized with ethidium and quantified by densitometry. NR1 1XX transcript expression was calculated as a proportion of the NR1 1XX + NR1 0XX total. Values were significantly lower in AD cases than in controls in mid‐cingulate cortex, p < 0.01, superior temporal cortex, p < 0.01 and hippocampus, p ∼ 0.05. Cortical proportionate NR1 1XX transcript expression was invariant over the range of ages and areas of controls tested, at ∼50%. This was also true for AD motor and occipital cortex. Proportionate NR1 1XX expression in AD cingulate and temporal cortex was lower at younger ages and increased with age: this regression was significantly different from that in the homotropic areas of controls. Variations in NR1 N‐terminal cassette expression may underlie the local vulnerability to excitotoxic damage of some areas in the AD brain. Alternatively, changes in NR1 mRNA expression may arise as a consequence of the AD disease process.