β‐<i>N</i>‐Oxalylamino‐L‐Alanine Action on Glutamate Receptors

Ross, Stephen M.; Roy, Dwijendra N.; Spencer, Peter S.

doi:10.1111/j.1471-4159.1989.tb11762.x

Cited by 97 publications

(42 citation statements)

References 22 publications

(14 reference statements)

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“…BMAA (an iGluR agonist) might inhibit AtGLR function but via a different mechanism. In animal systems, non-native agonists such as BMAA, can impair iGluR function because often iGluRs remain sensitized to these non-native ligands (Ross et al, 1989). In contrast, animal iGluRs become desensitized to the native agonist, Glu.…”

Section: Discussionmentioning

confidence: 99%

“…To further explore the targets of AtGLR function in plants, we tested whether other compounds known to block iGluR function in animals could also block aspects of Ara-bidopsis growth and development. Several of these iGluR agonists are plant-derived products: kainate (KA; Monaghan et al, 1989;Bettler and Mulle, 1995) made by seaweed (Digenea simplex); ␤-N-oxalylamino-l-alanine (Ross et al, 1989) made by chickpeas (Lathyrus sp. ), and BMAA (Copani et al, 1991) made by cycads.…”

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confidence: 99%

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Arabidopsis Mutants Resistant to S(+)-β-Methyl-α, β-Diaminopropionic Acid, a Cycad-Derived Glutamate Receptor Agonist

et al. 2000

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Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are the predominant neuroreceptors in the mammalian brain. Genes with high sequence similarity to animal iGluRs have been identified in Arabidopsis. To understand the role of Arabidopsis glutamate receptor-like (AtGLR) genes in plants, we have taken a pharmacological approach by examining the effects of BMAA [S(ϩ)-␤-methyl-␣, ␤-diaminopropionic acid], a cycad-derived iGluR agonist, on Arabidopsis morphogenesis. When applied to Arabidopsis seedlings, BMAA caused a 2-to 3-fold increase in hypocotyl elongation and inhibited cotyledon opening during early seedling development. The effect of BMAA on hypocotyl elongation is light specific. Furthermore, BMAA effects on early morphogenesis of Arabidopsis can be reversed by the simultaneous application of glutamate, the native iGluR agonist in animals. To determine the targets of BMAA action in Arabidopsis, a genetic screen was devised to isolate Arabidopsis mutants with a BMAA insensitive morphology (bim). When grown in the light on BMAA, bim mutants exhibited short hypocotyls compared with wild type. bim mutants were grouped into three classes based on their morphology when grown in the dark in the absence of BMAA. Class-I bim mutants have a normal, etiolated morphology, similar to wild-type plants. Class-II bim mutants have shorter hypocotyls and closed cotyledons when grown in the dark. Class-III bim mutants have short hypocotyls and open cotyledons when grown in the dark, resembling the previously characterized constitutively photomorphogenic mutants (cop, det, fus, and shy). Further analysis of the bim mutants should help define whether plant-derived iGluR agonists target glutamate receptor signaling pathways in plants.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Arabidopsis Mutants Resistant to S(+)-β-Methyl-α, β-Diaminopropionic Acid, a Cycad-Derived Glutamate Receptor Agonist

et al. 2000

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“…In contrast to BMAA, BOAA ingestion in animals and humans could induce neurodegeneration in a condition called neurolathyrism, but this disorder does not resemble ALS-PDC (Ross et al 1989). Similarly, neither cycasin nor MAM give ALS-PDC-like phenotypes (for a review, see Kurland 1972).…”

Section: Introductionmentioning

confidence: 99%

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Tabata

Wilson

et al. 2008

Neuromol Med

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Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which β-sitosterol β-D-glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC.

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“…17 The increase of glutamate may, in turn, cause competitive inhibition of high-and low-affinity glutamate transport, which is supposed to be a primary mechanism by which neurotransmitters are removed from the synaptic cleft. 17,35,36 Studies have shown that there is an interdependence among various associated receptor systems within the CNS, 18 hence further studies were carried out to investigate the effect of long-term administration of lathyrus on dopamine, cholinergic and benzodiazepine receptors. Rats exposed to 50% low or high toxin lathyrus diet and guinea pigs exposed to 50% or 80% lathyrus diet were found to have a significant increase in [ 3 H]spiperone binding to striatal regions, which may be playing a role in modulating the motor behaviour.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 In vitro studies have shown that β-L-ODAP selectively binds to the non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, which are of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or quinsqualate (QA) type and inhibit the low and high glutamate uptake systems in synaptosomes. 17,18 Oral administration of nonconvulsant doses of β-L-ODAP to rats increases the cerebellar cyclic guanosine monophosphate (cGMP) level and induces downregulation of non-NMDA glutamate receptors in the frontal cortex. 19,20 However, little is known about the cellular mechanism of β-L-ODAP excitotoxicity on glutamate and other related neuroreceptors on systemic administration of lathyrus pulse.…”

Section: Introductionmentioning

confidence: 99%

Comparative effect of dietary administration of Lathyrus sativus pulse on behaviour, neurotransmitter receptors and membrane permeability in rats and guinea pigs

Amba

Seth

Ali

et al. 2002

J of Applied Toxicology

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Neurolathyrism, an upper motor neuron disease, has been thought to be caused by long-term dietary consumption of lathyrus pulse, which contains the toxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid. Earlier behavioural studies employing oral feeding of lathyrus pulse to animals has been conducted without evaluating the biochemical toxicity potential. In the present investigation the effect of dietary feeding of 10%, 50% and 80% lathyrus pulse to rats and guinea pigs for 3 months on neurobehavioural parameters, including locomotor activity, inclined plain test and neurotoxicological parameters such as neurotransmitter receptor binding, Ca(2+) influx and membrane fluidity, was investigated. Exposure of 50% low and high toxin lathyrus to rats did not cause any significant change in locomotor activity, whereas guinea pigs at the same dosage regimen of high toxin lathyrus showed significant lowering of inclined plain test scores. Furthermore, studies of neuroreceptor binding in rats fed 50% low and high toxin lathyrus showed significant changes in glutamate, dopamine and muscarinic receptors, whereas the benzodiazepine receptor elicited no change. Guinea pigs, on the other hand, fed 50% and 80% lathyrus in the diet showed significant changes in glutamate, dopamine, muscarinic and benzodiazepine receptors. Interestingly, significant elevation in intracellular calcium with a concomitant increase in membrane fluidity was observed in rats (50% low and high toxin) and guinea pigs (50% and 80%) fed a lathyrus diet. These results indicate that although both species (rats and guinea pigs) are susceptible to neurochemical changes on exposure to lathyrus, locomotor changes are only noticed in guinea pigs. Thus, guinea pigs may be more prone to lathyrus toxicity and may serve as a sensitive animal model compared with rats.

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β‐N‐Oxalylamino‐L‐Alanine Action on Glutamate Receptors

Cited by 97 publications

References 22 publications

Arabidopsis Mutants Resistant to S(+)-β-Methyl-α, β-Diaminopropionic Acid, a Cycad-Derived Glutamate Receptor Agonist

Arabidopsis Mutants Resistant to S(+)-β-Methyl-α, β-Diaminopropionic Acid, a Cycad-Derived Glutamate Receptor Agonist

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS–PDC Phenotype

Comparative effect of dietary administration of Lathyrus sativus pulse on behaviour, neurotransmitter receptors and membrane permeability in rats and guinea pigs

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