MK-801 pretreatment enhances N-methyl-d-aspartate-mediated brain injury and increases brain N-methyl-d-aspartate recognition site binding in rats

McDonald, J. W.; Silverstein, Faye S.; Johnston, Michael V.

doi:10.1016/0306-4522(90)90377-g

Cited by 88 publications

(22 citation statements)

References 32 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9). This result is consistent with the literature demonstrating that treatment with NMDA antagonists produces up-regulation of the NMDA receptor complex as measured by an increase in the B max of NMDA receptor binding sites (McDonald et al, 1990; Figure 8. Volcano plot illustrating the significant gene expression changes in the thalamus 2 h after ketamine treatment.…”

Section: In Situ Hybridization (In Vivo and In Vitro)supporting

confidence: 91%

Systems biology approaches for toxicology

Slikker

Paule

Wright

et al. 2007

J of Applied Toxicology

View full text Add to dashboard Cite

Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N-methyl-D-aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death. It is proposed that continuous blockade of NMDA receptors in the developing brain by NMDA antagonists such as ketamine (a dissociative anesthetic) causes a compensatory up-regulation of NMDA receptors, which makes the neurons bearing these receptors subsequently more vulnerable (e.g. after ketamine washout), to the excitotoxic effects of endogenous glutamate: the up-regulation of NMDA receptors allows for the accumulation of toxic levels of intracellular Ca(2+) under normal physiological conditions. Systems biology, as applied to toxicology, provides a framework in which information can be arranged in the form of a biological model. In our ketamine model, for example, blockade of NMDA receptor up-regulation by the co-administration of antisense oligonucleotides that specifically target NMDA receptor NR1 subunit mRNA, dramatically diminishes ketamine-induced cell death. Preliminary gene expression data support the role of apoptosis as a mode of action of ketamine-induced neurotoxicity. In addition, ketamine-induced cell death is also prevented by the inhibition of NF-kappaB translocation into the nucleus. This process is known to respond to changes in the redox state of the cytoplasm and has been shown to respond to NMDA-induced cellular stress. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be carried out, biological models have been established in an iterative manner to allow for the confirmation of biological pathways underlying NMDA antagonist-induced cell death in the developing nonhuman primate and rodent. Published in 2007 John Wiley& Sons, Ltd.

show abstract

Section: In Situ Hybridization (In Vivo and In Vitro)supporting

confidence: 91%

Systems biology approaches for toxicology

Slikker

Paule

Wright

et al. 2007

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…That the glutamate receptors appear to respond briskly to PCP would imply a high turnover of NMDA and kainate receptors, and a close coupling between the density of glutamate receptors and synaptic activity. Similar data to these have been previously reported in the newborn rat (7 days old), where a single administration of MK801 produces NMDA upregulation sustained to 24 hours postinjection, and this upregulation was associated with increased sensitivity to NMDA-induced neurotoxicity (McDonald et al, 1990). The assumption that PCP is substantially altering glutamate release selectively and uniquely in regions of the hippocampus is a hypothesis derived from these data, and requires direct demonstration in future studies.…”

Section: Discussionsupporting

confidence: 79%

Phencyclidine produces changes in NMDA and kainate receptor binding in rat hippocampus over a 48-hour time course

Gao

Tamminga

1996

Synapse

View full text Add to dashboard Cite

Phencyclidine (PCP) is a psychotomimetic drug associated with acute and delayed mental effects in normal humans and psychosis exacerbation in already psychotic schizophrenic individuals. We have previously described a dose-sensitive, delayed action of PCP on regional cerebral metabolism in the rat which occurs over 48 hours and a late (24 hour) change in N-methyl-d-aspartate (NMDA) and kainate binding in hippocampal areas. Now, we report the complex time course of PCP action on NMDA-sensitive glutamate receptor binding in rat in distinct subregions of the hippocampus extending over 48 hours. Selectively, in the hippocampal CA1 region, a single dose of PCP (8.6 mg/kg) produced an increase in receptor binding at 12 hours (+24%), sustained to 24 hours (+29%) compared with the 3 hour post-PCP value (-15%) and then a return to control levels of receptor binding at 48 hours. Other regions of hippocampus showed distinctive time-dependent changes in NMDA-sensitive glutamate receptor binding as well. In addition, PCP produced a change in kainate receptor binding in the dentate gyrus across the 48-hour time period. In other representative brain regions, PCP did not alter NMDA or kainate binding over the same time course. This extended neurochemical effect of PCP on glutamate receptors in rat hippocampus parallels, in time, certain delayed psychological actions of PCP in humans and thus may be relevant to psychosis, especially to PCP-induced psychosis.

show abstract

“…Thus, we found two possible neurotransmitter receptor alterations that could contribute to enhanced neuronal excitability: a reduction in IAA receptor binding and an increase in the ratio of NMDA and glycine-type EAA receptors to PCP-type receptors within the NMDA receptor-operated channel. Although this is the first report of an increase in the ratio of NMDA receptors to PCP receptors in hippocampus from patients with TLE, a similar alteration in the NMDA receptorlchannel complex was observed in animal experiments, described below [49,503. This change could contribute to enhanced vulnerability of the TLE hippocampus to progressive neuronal injury.…”

Section: Discussionmentioning

confidence: 69%

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy

McDonald

Garofalo

Hood

et al. 1991

Annals of Neurology

209

View full text Add to dashboard Cite

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.

show abstract

MK-801 pretreatment enhances N-methyl-d-aspartate-mediated brain injury and increases brain N-methyl-d-aspartate recognition site binding in rats

Cited by 88 publications

References 32 publications

Systems biology approaches for toxicology

Systems biology approaches for toxicology

Phencyclidine produces changes in NMDA and kainate receptor binding in rat hippocampus over a 48-hour time course

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy

Contact Info

Product

Resources

About