Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy

Geddes, James W.; Gahan, Leslie D.; Cooper, Suzanne M.; Kim, Ronald C.; Choi, BongKyoo; Cotman, Carl W.

doi:10.1016/0014-4886(90)90125-c

Cited by 106 publications

(34 citation statements)

References 31 publications

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“…Reports include loss of kainic acid (KA) and NMDA receptors in the most sclerotic regions of the hippocampus (56)(57)(58), possibly due to neuronal loss and similar to the findings of our study. However, elevations of a-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA), KA, and NMDA receptors in selective areas of the HF also were reported, even including in CA1 (49,(56)(57)(58)(59). The probable selective increase in excitatory amino acid receptors in certain areas of the HF suggests that enhanced sensitivity to excitatory amino acids may be an important component in the pathophysiology of temporal lobe epilepsy.…”

Section: Fig 2 Binding Of the Muscarinic Antagonistsupporting

confidence: 91%

Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis

Pennell¹,

Burdette²,

Ross

et al. 1999

Epilepsia

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Summary:Purpose: Prior single-photon emission tomography studies showed losses of muscarinic acetylcholine receptor (MAChR) binding in patients with refractory mesial temporal lobe epilepsy. Experimental animal studies demonstrated transient losses of MAChR due to electrically induced seizures originating in the amygdala. However, the relations between cholinergic synaptic markers, seizures, and underlying neuropathology in human temporal lobe epilepsy are unknown. We tested the hypotheses that human brain MAChR changes are attributable to hippocampal sclerosis (HS), and that HS resembles axon-sparing lesions in experimental animal models.Methods: We measured MAChR binding-site density, an intrinsic neuronal marker, within the hippocampal formation (HF) in anterior temporal lobectomy specimens from 10 patients with HS and in 10 autopsy controls. Binding-site density of the presynaptic vesicular acetylcholine transporter (VAChT) was measured as a marker of extrinsic cholinergic afferent integrity. MAChR and VAChT results were compared with neuronal cell counts to assess their relations to local neuronal losses.Results: Reduced MAChR binding-site density was demonstrated throughout the HF in the epilepsy specimens compared with autopsy controls and correlated in severity with reductions in cell counts in several HF regions. In contrast to MAChR, VAChT binding-site density was unchanged in the epilepsy specimens compared with autopsy controls.Conclusions: Reduction in MAChR binding in HS is attributable to intrinsic neuronal losses. Sparing of afferent septa1 cholinergic terminals is consistent with the hypothesis that an excitotoxic mechanism may contribute to the development of HS and refractory partial epilepsy in humans.

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Section: Fig 2 Binding Of the Muscarinic Antagonistsupporting

confidence: 91%

Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis

Pennell¹,

Burdette²,

Ross

et al. 1999

Epilepsia

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“…In mice, memory deficits are localized to spatial memory tasks, but not activity levels, suggesting that hippocampal memory function is involved 9 . Similar behavioral deficits are implicated in other memory disorders such as Alzheimer’s-type dementia 10, 11–13 .…”

Section: Introductionmentioning

confidence: 68%

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

Provencio

Swank

et al. 2016

Brain, Behavior, and Immunity

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Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

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“…13,14 By contrast, NMDA-mediated postsynaptic potentials are probably decreased in CA2 pyramidal neurons, and anatomical studies have reported decreased or variable NMDA receptor labeling in Ammon's horn subfields. [15][16][17][18][19][20] Hence, studies of TLE patients support the concept that NMDA receptor activity is increased in dentate granule cells and decreased in pyramidal neurons of sclerotic hippocampi. It is unclear, however, whether the differences in hippocampal NMDAmediated responses can be attributed to changes in the subunit composition of NMDA receptors, and whether there are differences in receptor subunit mRNA levels between HS and non-HS cases.…”

mentioning

confidence: 63%

HippocampalN-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients

et al. 1999

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Altered distribution of excitatory amino acid receptors in temporal lobe epilepsy

Cited by 106 publications

References 31 publications

Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis

Muscarinic Receptor Loss and Preservation of Presynaptic Cholinergic Terminals in Hippocampal Sclerosis

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors

HippocampalN-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients

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