Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine

Oliveira, Diogo Lösch de; Horn, Joel Felipe; Rodrigues, Juliana; Frizzo, Marcos Emílio dos Santos; Moriguchi, Emílio Hideyuki; Souza, Diogo O.; Wofchuk, Susana Tchernin

doi:10.1016/j.brainres.2004.05.033

Cited by 57 publications

(65 citation statements)

References 50 publications

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“…Recently, Urd has been found to act as an antiepileptogen in hippocampal kindling models (Zhao et al 2006(Zhao et al , 2008 . In addition, Guo prevented seizures induced by quinolinic acid and other glutamatergic agents (De Oliveira et al 2004 ;Schmidt et al 2000 ) . These data suggest that Urd and Guo also have antiepileptic potential.…”

Section: Epilepsymentioning

confidence: 95%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

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Section: Epilepsymentioning

confidence: 95%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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“…However, nonAdo nucleosides, such as Guo, Ino and Urd, may also decrease the EC level of the excitatory neurotransmitter glutamate and/or increase GABAergic inhibition [88][89][90] and participate in pathophysiological processes of epilepsy [58][59][60][61][62][63][64]. Consequently, not only Ado [27,33,[65][66][67] but also nonAdo nucleosides (e.g., Ino, Guo and Urd) and their derivatives may be potential drugs in the treatment of different types of epilepsies.…”

Section: Modulatory Role Of Nucleosides On Epileptic Activitymentioning

confidence: 99%

“…Guanosine also has antiseizure effects in rodent epilepsy models, most likely via Guo-induced modulation of the glutamatergic system [60][61][62][368][369][370][371]. Guo may bind to its putative (uncloned) G-protein-coupled receptors in the brain [50,51].…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

“…Among their diverse neuromodulatory functions, nucleosides may have a role in the modulation of epileptic activity as well [27,33,[58][59][60][61][62][63][64][65][66][67][68][69]. Therefore, drugs or nucleoside derivatives effective on nucleoside uptake, nucleoside receptors or nucleoside metabolism may be useful for the treatment of different diseases in the CNS, such as epilepsy [31].…”

Section: Introductionmentioning

confidence: 99%

“…Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants have also been shown to be effective in treating epileptic seizures [27,32,65,67]. In addition, not only Ado but also non-Ado nucleosides (e.g., Guo, Ino and Urd) showed antiseizure/anticonvulsant activity in various epilepsy models and are potential candidates involved in Cyt: cytosine; DAG: diacylglycerol; ENT1/ENT2/ENT3/ENT4 transporters: ENT1/ENT2/ENT3/ENT4 subtype of equilibrative nucleoside transporters; "ei": equilibrative, NBTI (S-(4-nitrobenzyl)-6-thioinosine) insensitive type of ENTs; "es": equilibrative, NBTI sensitive type of ENTs; Gi, G0, Gs, Gq, Golf: G-proteins; GIRK: G-protein-dependent inwardly rectifying K + channels; Guo: guanosine; IP3: inositol 1,4,5-triphosphate; PLC: phospholipase C; Urd: uridine epilepsy [58,[60][61][62][63][64]70]. In this review, we summarize what is known about the nucleoside system in the brain in relation to its potential application against epileptic seizures.…”

Section: Introductionmentioning

confidence: 99%

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The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation

Ghebranious

Giampietro

Wesbrook

et al. 2007

American J of Med Genetics Pt A

112

111

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Many multiple congenital anomalies (MCA) are caused by recombination between homologous segmental duplications. In this report, we describe a novel “de novo” microdeletion in male monozygotic twins presenting with aortic valve abnormality, seizure disorder, and mild mental retardation. Using array based comparative genomic hybridization, we mapped the microdeletion to the short arm of chromosome 16 at 16p11.2 and refined it using hemizygosity mapping to about 593 kb, a region that overlaps with 24 genes. The most probable mechanism for this microdeletion is through a specific intrachromosomal recombination between two, nearly identical, segmental duplications each spanning 147 kb that are flanking the microdeletion. Based on the phenotypes presented in the twins and what is known about the genes within the 16p11.2 microdeletion, we identified several genes that are strong candidates for the normal development of the aortic valve, as well as the development of seizure disorder and mental retardation. © 2007 Wiley‐Liss, Inc.

show abstract

Quinolinic acid promotes seizures and decreases glutamate uptake in young rats: reversal by orally administered guanosine

Cited by 57 publications

References 50 publications

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

The Antiepileptic Potential of Nucleosides

A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation

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