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Variant Forms of Neuronal Glutamate Transporter Sites in Alzheimer's Disease Cerebral Cortex
Author(s) -
Scott Heather L.,
Tannenberg Anthony E. G.,
Dodd Peter R.
Publication year - 1995
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.1471-4159.1995.64052193.x
Subject(s) - glutamate receptor , cerebral cortex , alzheimer's disease , excitotoxicity , hippocampal formation , degenerative disease , motor cortex , posterior cingulate , pathology , central nervous system disease , cortex (anatomy) , medicine , biology , endocrinology , neuroscience , biochemistry , receptor , disease , stimulation
The displacement of Na + ‐dependent d ‐[ 3 H]‐aspartate binding by unlabeled d ‐aspartate or the inhibitors dl ‐ threo ‐β‐hydroxyaspartate, l ‐cysteate, l ‐glutamate, dihydrokainate, dl ‐α‐aminoadipate, α‐methyl‐ dl ‐glutamate, and 1‐aminocyclobutane‐ cis ‐1,3‐dicarboxylate was used to characterize the high‐affinity glutamate/aspartate uptake site in human cerebral cortex. Synaptosomal membranes were prepared from tissue obtained at autopsy from nondemented control, Alzheimer's disease (AD), and diffuse Lewy body disease (DLBD) cases. Areas that are damaged in AD (midtemporal, frontal, caudal cingulate, and hippocampal cortices) were compared with those that are spared (occipital and motor cortices). Profiles of the affinities ( K a values) of the ligands showed that areas spared from damage in AD cases differed significantly from equivalent areas in control ( p < 0.001) and DLBD ( p < 0.001) cases and also from areas susceptible to damage in the same AD cases ( p < 0.001). Areas susceptible to damage in AD showed comparable profiles across the three case groups ( p = 0.980). The glutamate/aspartate uptake site may be regionally variant in AD cases, and this may underlie local excitotoxicity. d ‐[ 3 H]Aspartate binding site density was significantly lower in both dementia groups (control vs. AD, p < 0.001; control vs. DLBD, p = 0.009; but AD vs. DLBD, p = 0.528); within‐group differences were not significant (control, p = 0.874; AD, p = 0.285; DLBD, p = 0.741).