ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
An excitotoxin is most effective when neurons of interest in a given region are more susceptible to its toxic effects than others, thereby inducing a relatively selective lesion. Generally, the pattern of damage caused by different excitotoxins is related to the types of glutamate receptors found in the target area, and perhaps even the specific RECEPTOR SUBUNITS which form these receptors. A good example of this is the use of AMPA in the rat BASAL FOREBRAIN, where it can be used to target CHOLINERGIC neurons, if the concentration and volume are titrated correctly. Histochemical and lesion data suggest that this is linked to the high expression of the GluR4 receptor subunit in AMPA receptors in this area. Unfortunately, excitotoxins are never generally more than partially selective neurotoxic agents, and any selectivity which is obtained is critically dependent on the concentration of the infusion. The more recent immunotoxin approach, which uses ribosomeinactivating proteins such as SAPORIN, conjugated to specific receptor antibodies, is a more selective means of making brain lesions.
Outdoor Emissions
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Excitotoxicity is another potential downstream mechanism. OS enhances excitotoxin effects, such as delayed calcium deregulation (DCD) which “precedes and predicts” cell death791; so does mitochondrial calcium accumulation.791 Ca2+ combines with protein kinase A/C and when phosphorylated increases sensitivity up to 1000 times. Moreover, excitotoxins in turn cause OS and mitochondrial impairment, which is a major mediator of excitotoxin neurotoxicity.792 The development of excitotoxic neurotoxicity leads to wide spread inability to tolerate normal environmental incitors such as food, mold, and other chemical toxicity and sensitivity preventing the patient from functioning well in society. This is because minute exposures, that is, perfumes, chemical cleaning agents, and various other odors of daily living will cause reactions. The resulting entity is chemical sensitivity.
Pharmacologic agents directed at the treatment of pain associated with maladaptive neuronal plasticity
Published in Expert Opinion on Pharmacotherapy, 2022
Joseph V. Pergolizzi, Giustino Varrassi, Peter Magnusson, Frank Breve, Robert B. Raffa, Paul J. Christo, Maninder Chopra, Antonella Paladini, Jo Ann LeQuang, Kailyn Mitchell, Flaminia Coluzzi
Like ketamine, memantine is an N-methyl-D-aspartic acid receptor (NMDAR) antagonist but should be considered separately in this context. Excitotoxicity may trigger neuronal pathways of cell death that have been implicated in neuropathic pain and neurodegenerative diseases [61]. A ‘death pathway’ is formed when excessive NMDA receptor stimulation occurs that causes receptor hyperactivity, which, depending on its level of intensity, may lead to necrosis or apoptosis [61]. For that reason, NMDA receptor antagonists could be a pharmacologic target to help reduce excitotoxic neuronal death. Memantine is an open-channel blocker that can selectively block excessive NMDA receptor activity with minimal disruption of normal activity, i.e. fewer side effects [61]. New memantine moieties exhibit multiple neuroprotective effects including defense against glutamate-induced excitotoxicity, oxidative stress, and hypoxic injury and inhibited the release of pro-inflammatory cytokines from the microglia [62].
Dietary omega-3 fatty acids prevent neonatal seizure-induced early alterations in the hippocampal glutamatergic system and memory deficits in adulthood
Published in Nutritional Neuroscience, 2022
Júlia D. Moreira, Letícia Vicari Siqueira, Alexandre P. Müller, Lisiane O. Porciúncula, Lúcia Vinadé, Diogo O. Souza
The fundamental role of glutamate for brain development, maturation and functions related to memory / learning processes and synaptic plasticity is well known, in addition to being involved in brain aging [5,6,9]. However, glutamate can become toxic to brain cells in a process named ‘excitotoxicity’ [6,9]. Glutamatergic excitotoxicity occurs when excess glutamate is release in the synaptic cleft and it overcomes the capacity of glial glutamate transporters to remove it from the synapse, which leads to NMDA receptor hyperactivation, excess calcium influx and the loss of neuronal homeostasis, culminating with cell death and loss of function [10,11]. Excitotoxicity is involved in pathological processes associated with neurological diseases such as Alzheimer's disease, Parkinson's disease, and epilepsy [10–12].
Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced neuronal cell death by attenuating mitochondrial dysfunction
Published in Nutritional Neuroscience, 2018
Mi Hye Kim, Ju-Sik Min, Joon Yeop Lee, Unbin Chae, Eun-Ju Yang, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Glutamate, which is one of the main neurotransmitters of the CNS, is engaged in neuronal transmission, development, differentiation, and plasticity. However, excessive glutamate accumulation can cause abnormal depolarization of neurons, excitotoxicity; it leads to neuronal cell death.17 Especially, excitotoxicity causes many neurodegenerative disease, including Huntington's disease, Alzheimer's disease, lateral amyotrophic sclerosis, Parkinson's disease, and stroke or traumatic brain injury. Glutamate excitotoxicity is induced through activation of NMDA, AMPA receptor or non-glutamate receptor. HT-22 cell line, which is an immortalized mouse hippocampal cell line, is widely used to study the non-receptor mediated oxidative glutamate toxicity through GSH depletion and ROS accumulation.18 In addition, several studies suggest that mitochondrial oxidative stress and dysfunction play crucial role in promoting glutamate-induced cell death in HT-22.19–21 Therefore, Glutamate-mediated excitotoxicity, which is associated with ROS accumulation, is hypothesized to be a major contributor to pathological cell death in the mammalian CNS and to be involved in many acute and chronic brain diseases. In this study, we showed that Ole, isolated from FR, protected HT-22 hippocampal neuronal cells from glutamate-induced oxidative stress. In addition, as the protective molecular mechanism, this study showed that Ole inhibits glutamate-induced neuronal cell death through attenuating mitochondrial dysfunction with mitochondrial fragmentation and characteristic apoptosis.
Related Knowledge Centers
- Ampa Receptor
- Glutamate Receptor
- Glutamic Acid
- Nmda Receptor
- Phospholipase
- Neurotransmitter
- Cell Surface Receptor
- Neuron
- Calcium In Biology
- Cell