Alterations in L-Glutamate Binding in Alzheimer's and Huntington's Diseases

Greenamyre, J. Timothy; Penney, JB; Young, A. Byron; D’Amato, Constance J.; Sp, Hicks; Shoulson, Ira

doi:10.1126/science.2858129

Cited by 325 publications

(93 citation statements)

References 42 publications

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“…The neurotransmitter utilized in corticocortical circuits is believed to be an excitatory amino acid (Baughman and Gilbert,198 1;Fonnum et al,198 1;Hicks and Geddes,198 1). Recent studies have demonstrated in AD the loss of both glutamate (Greenamyre et al, 1985) and aspartate (Palmer et al, 1986) receptors in the neocortex, a profound decrease in glutamate levels in the terminal field of the perforant pathway (Hyman et al, 1986) and the presence of NFT in glutamate-immunoreactive neurons (Maragos et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices

Lewis¹,

Campbell²,

Terry³

et al. 1987

J. Neurosci.

550

270

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The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron- wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.

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Section: Discussionmentioning

confidence: 99%

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices

Lewis¹,

Campbell²,

Terry³

et al. 1987

J. Neurosci.

550

270

View full text Add to dashboard Cite

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“…66 More recently, decreases in glutamate receptors from the caudate and putamen isolated from HD patients were reported. 67 These findings probably reflected the loss of cells in the same brain regions that typically occur in HD. Bioenergetic defects, such as mitochondrial metabolic dysfunction, have also been reported in HD brain.…”

Section: Huntington's Diseasementioning

confidence: 95%

The relationship between excitotoxicity and oxidative stress in the central nervous system

Bondy

LeBel

1993

Free Radical Biology and Medicine

153

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Abstract-Excitotoxicity and oxidative stress are two phenomena that have been repeatedly described as being implicated in a wide range of disorders of the nervous system. Such disorders include several common idiopathic neurological diseases, traumatic brain injury, and the consequences of exposure to certain neurotoxic agents. While there is evidence that metabolic derangements can lead to these adverse processes, and that these processes may synergize in their damaging effects, the degree of interdependence, and the causal relation between them is not clear. The intent of this review is to delineate potential mechanisms which may unit hyperexcitation to the excessive generation of reactive oxygen species. The degree of linkage between these events appears rather strong. It is likely that excitoxicity frequently leads to a pro-oxidant condition but that high rates of generation of reactive oxygen species are not invariably accompanied by a hyperexcited neuronal state Both excitoxic and 'oxidotoxic' states result from the failure of normal compensatory antiexcitatory and antioxidant mechanisms to maintain cellular homeostasis.

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“…Several neurotransmitters, including cholinergic markers, noradrenergic markers, somatostatin, GABA, 5-HT, glutamate, neuropeptide Y, and CRF, are all reportedly diminished in AD, with apparent sparing of VIP, CCK, TRH, and LHRH content (see 5, 33, 63,64,78,103,115). Both cholinergic markers and many of the putative peptide transmitters have been found within or near NPs (131).…”

Section: Neurochemical Alterations In Alzheimer's Diseasementioning

confidence: 99%