Neurotoxic and neurotrophic effects of chronic N-methyl-d-aspartate exposure upon mesencephalic dopaminergic neurons in organotypic culture

  title={Neurotoxic and neurotrophic effects of chronic N-methyl-d-aspartate exposure upon mesencephalic dopaminergic neurons in organotypic culture},
  author={Brian G. M. Dickie and C. J. Holmes and Susan A Greenfield},
Co-culture with the striatum attenuates N-methyl-D-aspartate cytotoxicity in dopaminergic neurons of rat mesencephalic slice cultures.
It is suggested that the projection of rat mesencephalic DA neurons to the striatum attenuates the NMDA cytotoxicity in DA neurons themselves.
N-Methyl-d-aspartate Preconditioning Prevents Quinolinic Acid-Induced Deregulation of Glutamate and Calcium Homeostasis in Mice Hippocampus
Cellular and molecular mechanisms involved on NMDA preconditioning and neuroprotection were investigated in mice treated with NMDA 24 h before QA insult, demonstrating that calcium and glutamate are involved in NMDA-induced preconditionsing.
Glutamate and Neurotoxicity
The toxic effects of glutamate exposure on neurons were first recognized nearly half a century ago, when Lucas and Newhouse observed that subcutaneous administration of glutamate caused loss of
Opposing Effects of Excitatory Amino Acids on Chick Embryo Spinal Cord Motoneurons: Excitotoxic Degeneration or Prevention of Programmed Cell Death
It is indicated for the first time that early activation of NMDA receptors in developing avian MNs in vivo has a trophic, survival-promoting effect, inhibiting PCD by a target-independent mechanism that involves NMDA receptor downregulation.
Effects of excitatory amino acids on neuromuscular development in the chick embryo
Embryos with motoneuronal depletion induced by NMDA showed a delayed impairment of later neuromuscular development with the appearance of degenerative changes in surviving MNs and apoptosis of skeletal muscle cells, and some of the alterations reported here are similar to those described in MN diseases.
Bioactivity of a peptide derived from acetylcholinesterase in hippocampal organotypic cultures
The bioactivity associated with the AChE-peptide sequence may account for the non-cholinergic actions of A ChE, whilst its neurotrophic-apoptotic-necrotic spectrum of action may be involved in the aetiology of neurodegenerative disorders such as Alzheimer’s disease.
Prolonged Inhibition of Glutamate Reuptake Down‐Regulates NMDA Receptor Functions in Cultured Cerebellar Granule Cells
The down‐regulation of the functional effects of glutamate was dependent on the duration of PDC exposure and was accompanied by a reduced NMDAR1 subunit expression and decreased [3H]MK‐801 binding, indicative of a pronounced structural rearrangement of NMDA receptors.
Proteomic Analysis of the Mice Hippocampus After Preconditioning Induced by N-Methyl-d-Aspartate (NMDA)
Proteomic analysis showed that the neuroprotection induced by NMDA preconditioning altered signaling pathways, cell energy maintenance and protein synthesis and processing, and may occur in a sense to attenuate the excitotoxicity process during the activation of neuroprotection promoted by NMda preconditionsing.
Role of Phosphatidylinositol-3 Kinase Pathway in NMDA Preconditioning: Different Mechanisms for Seizures and Hippocampal Neuronal Degeneration Induced by Quinolinic Acid
The study confirms that PI3K participates in the mechanism of protection induced by NMDA preconditioning against QA-induced seizures, and points to differential mechanisms regarding protection against a behavioral and cellular manifestation of neural damage.


Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists
It is reported that certain selective NMDA antagonists (AP7, CPP, MK-801, but not the preferential quisqualate antagonists CNQX and NBQX,8 provided short-term protection against MPP+ toxicity when coadministered into the substantia nigra.
N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells.
Among four glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate), only NMDA was able to provide a robust neuroprotection against glutamate toxicity, and it appears that the neuroprotective effects of NMDA are not due to NMDA receptor desensitization.
N-methyl-D-aspartate receptor-mediated neuroprotection in cerebellar granule cells requires new RNA and protein synthesis.
  • A. Marini, S. Paul
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1992
In cerebellar granule cells activation of NMDA receptors by glutamate can result in either neurotoxicity or neuroprotection, depending on the apparent degree of receptor stimulation.