In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice

Bernard-Hélary, Katy; Ardourel, Maryvonne; Hevor, T. K.; Cloix, Jean‐François

doi:10.1016/s0006-8993(01)03380-7

Cited by 19 publications

(34 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More than 60 years ago it was observed that domestic animals developed seizures after being fed bleached (agenized) flour [95]. The bleaching process oxidized methionine in the flour to MSO [96], and later investigations demonstrated that systemic administration of MSO to rats and mice inhibits GS and results in severe convulsive seizures [97-100]. Moreover, chronic infusion of MSO locally into the hippocampus of rats results in inhibition of GS, and subsequent recurrent seizures [17, 80].…”

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

“…However, the effects of MSO are not limited to GS inhibition, and it is possible that the convulsant properties of the chemical are caused by other mechanisms. For example, treatment of animals with MSO increases the content of glycogen in astrocytes [97] and depletes the tissue stores of glutathione [101]. Alterations in brain glutathione [102] and glycogen (discussed later) [98, 103] have been associated with seizures; however, the exact role of these compounds in epilepsy are not completely understood.…”

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

See 1 more Smart Citation

Roles of Glutamine Synthetase Inhibition in Epilepsy

et al. 2012

View full text Add to dashboard Cite

Glutamine synthetase (GS, E.C. 6.3.1.2) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer’s disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.

show abstract

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

Section: What Are the Metabolic And Functional Consequences Of Brain mentioning

confidence: 99%

Roles of Glutamine Synthetase Inhibition in Epilepsy

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Among the various epileptic or seizure-induced models, one of them is associated with both crisis and a specific increase in brain glycogen content [124, 125, 151-156]. This model corresponds to seizures induced by a derivative of methionine, namely methionine sulfoximine (MSO).…”

Section: Mso-induced Epilepsymentioning

confidence: 99%

Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission

Cloix

Hevor

2009

CMC

View full text Add to dashboard Cite

Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most “resistant” strain to methionine sulfoximine, while CBA/J is the most “sensitive” one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.

show abstract

“…As there is significant variability in drug metabolism among different strains of rats and mice, [6][7][8] pharmacokinetic data generated from one strain may be atypical and may not even represent the pharmacokinetic profile of most strains of that species.…”

Section: Introductionmentioning

confidence: 99%

In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor

Zhang¹,

Liu

Weller³

et al. 2010

Pharmacogenomics J

View full text Add to dashboard Cite

The clinical development of a candidate p38 kinase inhibitor was terminated because of its unexpectedly rapid clearance in human subjects. Its short halflife and metabolic profile in human beings were vastly different from that in rats, dogs, and monkeys characterized during routine pre-clinical studies. Mice generated the predominant drug (4-hydroxylated) metabolite produced in human beings, which was not found in other species. The data from a murine in vitro drug biotransformation assay that used liver extracts from 14 inbred mouse strains were analyzed by haplotype-based computational genetic analysis. This led to the identification of aldehyde oxidase-1 (AOX1) as the enzyme responsible for the rapid metabolism of this drug. Specific enzyme inhibitors and expressed recombinant enzymes were used to confirm that AOX catalyzed the formation of the 4-hydroxylated drug metabolite in mouse and man. Genetic variation within Aox1 regulated the level of hepatic Aox1 mRNA, AOX1 protein, and enzyme activity among the inbred strains. Thus, computational murine pharmacogenetic analysis can facilitate the identification and characterization of drug metabolism pathways that are differentially utilized by humans and other species.

show abstract

In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice

Cited by 19 publications

References 33 publications

Roles of Glutamine Synthetase Inhibition in Epilepsy

Roles of Glutamine Synthetase Inhibition in Epilepsy

Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission

In silico and in vitro pharmacogenetics: aldehyde oxidase rapidly metabolizes a p38 kinase inhibitor

Contact Info

Product

Resources

About