The Dietary Excitotoxins β‐<i>N</i>‐Methylamino‐<scp>l</scp>‐Alanine and β‐<i>N</i>‐Oxalylamino‐<scp>l</scp>‐Alanine Induce Necrotic‐ and Apoptotic‐Like Death of Rat Cerebellar Granule Cells

Staton, Penelope C.; Bristow, David R.

doi:10.1046/j.1471-4159.1997.69041508.x

Cited by 21 publications

(19 citation statements)

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“…This creates an endogenous reservoir of neurotoxin within the human body, capable of slow release into cerebral and other tissues during protein catabolism for years or decades after its consumption. In vivo (Spencer et al, 1987;Smith and Meldrum, 1990;Rakonczay et al, 1991;Chang et al, 1993;Santucci et al, 2009) and in vitro studies have reported that BMAA acts as a glutamate agonist onto spinal motoneurons (Rao et al, 2006) and cortical (Lobner et al, 2007) and cerebellar (Staton and Bristow, 1997) neurons. However, a detailed description of its actions on substantia nigra pars compacta (SNpc) dopaminergic cells (DAergic) is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Metabotropic Glutamate Receptor 1 Mediates the Electrophysiological and Toxic Actions of the Cycad Derivative β-N-Methylamino-l-Alanine on Substantia Nigra Pars Compacta DAergic Neurons

et al. 2010

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Amyotrophic lateral sclerosis-Parkinson dementia complex (ALS-PDC) is a neurodegenerative disease with ALS, parkinsonism, andAlzheimer's symptoms that is prevalent in the Guam population. ␤-N-Methylamino alanine (BMAA) has been proposed as the toxic agent damaging several neuronal types in ALS-PDC, including substantia nigra pars compacta dopaminergic (SNpc DAergic) neurons. BMAA is a mixed glutamate receptor agonist, but the specific pathways activated in DAergic neurons are not yet known. We combined electrophysiology, microfluorometry, and confocal microscopy analysis to monitor membrane potential/current, cytosolic calcium concentration (

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Section: Introductionmentioning

confidence: 99%

Metabotropic Glutamate Receptor 1 Mediates the Electrophysiological and Toxic Actions of the Cycad Derivative β-N-Methylamino-l-Alanine on Substantia Nigra Pars Compacta DAergic Neurons

et al. 2010

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“…3 mM BMAA- (Staton and Bristow, 1997) and 3 mM ACPD-induced death (results not shown) were not significantly greater than controls until 12 h of exposure.…”

Section: Measurement Of Glutamate- Bmaa- and Acpdinduced Cgc Deathmentioning

confidence: 73%

“…1993b; Toms et al, 1995). The CGCs used in our experiments were age 12-14 D1V, because this was optimal for studying glutamate-and BMAA.-induced CGC death (Staton and Bristow, 1997). To determine whether the lack of an mGluR-induced Ca 2~rise in CGCs age 12-14 DIV was due to limited expression of group I mGluRs, short ACPD and DHPG exposure experiments were also pei-formed in CGCs age 4 DIV.…”

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confidence: 99%

Role of Group III Metabotropic Glutamate Receptors in Excitotoxin‐Induced Cerebellar Granule Cell Death

Staton

Bristow

1998

Journal of Neurochemistry

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Abstract:The neuronal effects of the metabotropic glutamate receptor agonist (1 S,3R)-aminocyclopentane-1 ,3-dicarboxylic acid have been studied in cultured rat cerebellar granule cells, and compared with those of the endogenous excitotoxin glutamate, and the dietary excitotoxin /3-N-methylamino-L-alanine. Glutamate,~3-N-methylamino-L-alanine, and (1 S ,3R) -aminocyclopentane-1 ,3-dicarboxylic acid all caused concentration-dependent cerebellar granule cell death over a 24-h exposure period. The metabotropic antagonist (RS) -a-methyl-4-carboxyphenylglycine reduced glutamate-, /3-N-methylamino-L-alanine-, and (1 S ,3R)-aminocyclopentane-1 ,3-dicarboxylic acid-induced death by 50, 37, and 90%, respectively. (1 S ,3R) -Aminocyclopentane-1 ,3-dicarboxylic acid-induced death was unaffected by the group I antagonist (RS)-1 -aminoindan-1 ,5-dicarboxylic acid, increased by the group II antagonist ethylglutamic acid, and markedly decreased by the group Ill antagonist (RS) -amethylserine-O-phosphate. Neither (1 S ,3R) -aminocyclopentane-1 ,3-dicarboxylic acid nor the group I agonist (RS)-3,5-dihydroxyphenylglycine caused an increase in intracellular free calcium levels. The group Ill agonist L-(+)-2-amino-4-phosphonobutyric acid also induced concentration-dependent cerebellar granule cell death, and so it was suggested that the group Ill metabotropic glutamate receptors were responsible for (1 S,3R)-aminocyclopentane-1 ,3-dicarboxylic acid-induced death. Blocking these receptors with (RS) -a-methylserine-O-phosphate also prevented a proportion of glutamate-and /3-N-methylamino-L-alanineinduced death. Key Words: (1 S,3R)-Aminocyclopentane-1 ,3-dicarboxylic acid-/3-N-Methylamino-L-alanine-Rat cerebellar granule cells-Glutamate. J. Neurochem. 71, 1280Neurochem. 71, -1288Neurochem. 71, (1998.Glutamate is the principal excitatory neurotransmitter in the mammalian brain, where it activates both ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Tonotropic glutamate receptors are ligand-gated ion channels that comprise NMDA and a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) kainate subtypes (Monaghan et al., 1989). Overactivation of ionotropic receptors results in neuronal death via excitotoxicity , and some of the intracellular events that lead to death can be influenced by mGluRs (Pin and Duvoisin, 1995).mGluRs are coupled to U proteins, and this family of glutamate receptors comprises eight subtypes, to date, that are divided into three groups, based on their second messenger coupling, sequence similarity, and ligand selectivities (Pin and Duvoisin, 1995). Group I includes mGluRi and mGluR5, which are coupled to polyphosphoinositide (PPI) hydrolysis. mGluRs from groups II (mGluR2 and mGluR3) and III (mGluR4, mGluR6, mGluR7, and mGluR8) are negatively coupled to adenylate cyclase activity. In addition, an mGluR receptor coupled to phospholipase D has been identified in the hippocampus (Pellegrini-Giampetro et al., 1996). This coupling to disparate transduction pathways may underlie th...

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“…Both hypofunction and overstimulation of NMDAR can cause cell death. Blockade of NMDAR elicits apoptosis, while overstimulation of NMDAR can trigger either apoptosis or necrosis, depending on the intensity of receptor activation (Bonfoco et al, 1995; Staton and Bristow, 1997). Precisely, short exposure to low concentrations of glutamate or NMDA evokes apoptosis in cortical neurons (Leist et al, 1999), whereas intense exposure to high concentrations of NMDA or glutamate induces necrotic cell damage (Bano et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Serine racemase: a key player in apoptosis and necrosis

Canu

Ciotti

Pollegioni

2014

Front. Synaptic Neurosci.

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A fine balance between cell survival and cell death is required to sculpt the nervous system during development. However, an excess of cell death can occur following trauma, exposure to neurotoxins or alcohol, and some developmental and neurodegenerative diseases, such as Alzheimer's disease (AD). N-Methyl-D-aspartate receptors (NMDARs) support synaptic plasticity and survival of many neuronal populations whereas inappropriate activation may promote various forms of cell death, apoptosis, and necrosis representing the two extremes of a continuum of cell death processes both “in vitro” and “in vivo.” Hence, by identifying the switches controlling pro-survival vs. apoptosis and apoptosis vs. pro-excitotoxic outcome of NMDAR stimulation, NMDAR modulators could be developed that selectively block the cell death enhancing pro-survival signaling or synaptic plasticity mediated by NMDAR. Among these modulators, a role is emerging for the enzyme serine racemase (SR) that synthesizes D-serine, a key co-agonist with glutamate at NMDAR. This review summarizes the experimental evidence from “in vitro” neuronal cultures—with special emphasis on cerebellar granule neurons (CGNs)—and “in vivo” models of neurodegeneration, where the dual role of the SR/D-serine pathway as a master regulator of apoptosis and the apoptosis-necrosis shift will be discussed.

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The Dietary Excitotoxins β‐N‐Methylamino‐l‐Alanine and β‐N‐Oxalylamino‐l‐Alanine Induce Necrotic‐ and Apoptotic‐Like Death of Rat Cerebellar Granule Cells

Cited by 21 publications

References 40 publications

Metabotropic Glutamate Receptor 1 Mediates the Electrophysiological and Toxic Actions of the Cycad Derivative β-N-Methylamino-l-Alanine on Substantia Nigra Pars Compacta DAergic Neurons

Metabotropic Glutamate Receptor 1 Mediates the Electrophysiological and Toxic Actions of the Cycad Derivative β-N-Methylamino-l-Alanine on Substantia Nigra Pars Compacta DAergic Neurons

Role of Group III Metabotropic Glutamate Receptors in Excitotoxin‐Induced Cerebellar Granule Cell Death

Serine racemase: a key player in apoptosis and necrosis

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