دورية أكاديمية
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Creatine protects against the convulsive behavior and lactate production elicited by the intrastriatal injection of methylmalonate.

التفاصيل البيبلوغرافية
العنوان: Creatine protects against the convulsive behavior and lactate production elicited by the intrastriatal injection of methylmalonate.
المؤلفون: Royes LF; Department of Chemistry, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil., Fighera MR, Furian AF, Oliveira MS, da Silva LG, Malfatti CR, Schneider PH, Braga AL, Wajner M, Mello CF
المصدر: Neuroscience [Neuroscience] 2003; Vol. 118 (4), pp. 1079-90.
نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605074 Publication Model: Print Cited Medium: Print ISSN: 0306-4522 (Print) Linking ISSN: 03064522 NLM ISO Abbreviation: Neuroscience Subsets: MEDLINE
أسماء مطبوعة: Publication: [New York?] : Elsevier Science
Original Publication: Oxford, Elmsford, N. Y., Pergamon Press
مواضيع طبية MeSH: Creatine/*therapeutic use , Lactic Acid/*metabolism , Methylmalonic Acid/*toxicity , Seizures/*prevention & control, Animals ; Behavior, Animal ; Corpus Striatum/drug effects ; Corpus Striatum/injuries ; Disease Models, Animal ; Dizocilpine Maleate/pharmacology ; Dose-Response Relationship, Drug ; Excitatory Amino Acid Agonists/toxicity ; Excitatory Amino Acid Antagonists ; Male ; N-Methylaspartate/toxicity ; Phosphocreatine/metabolism ; Radiation-Protective Agents ; Rats ; Rats, Wistar ; Seizures/chemically induced ; Succinic Acid/pharmacology
مستخلص: Methylmalonic acidemias are metabolic disorders caused by a severe deficiency of methylmalonyl-CoA mutase activity, which are characterized by neurological dysfunction, including convulsions. It has been reported that the accumulating metabolite, L-methylmalonic acid (MMA), inhibits succinate dehydrogenase leading to ATP depletion in vitro, and that the intrastriatal injection of MMA induces convulsions through secondary NMDA receptor stimulation. In this study we investigated the effect of creatine (1.2, 3.6 and 12.0 mg/kg, (i.p.), [DOSAGE ERROR CORRECTED] succinate (1.5 micromol/striatum) and MK-801 (3 nmol/striatum) on the convulsions and on the striatal lactate increase induced by MMA (4.5 micromol/striatum) in rats. The effect of creatine on the striatal phosphocreatine content and on MMA-induced phosphocreatine depletion was also evaluated. Creatine, succinate and MK-801 pretreatment decreased the number and duration of convulsive episodes and the lactate increase elicited by MMA. Creatine, but not succinate, prevented the convulsions and the lactate increase induced by the direct stimulation of NMDA receptors. Acute creatine administration increased the total striatal phosphocreatine content and prevented MMA-induced phosphocreatine depletion. Our results suggest that MMA increases lactate production through secondary NMDA receptor activation, and it is proposed that the anticonvulsant effect of creatine against MMA-induced convulsions may be due to an increase in the phosphocreatine content available for metabolic purposes.
التعليقات: Erratum in: Neuroscience. 2004;125(2):533. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.
المشرفين على المادة: 0 (Excitatory Amino Acid Agonists)
0 (Excitatory Amino Acid Antagonists)
0 (Radiation-Protective Agents)
020IUV4N33 (Phosphocreatine)
33X04XA5AT (Lactic Acid)
6384-92-5 (N-Methylaspartate)
6LR8C1B66Q (Dizocilpine Maleate)
8LL8S712J7 (Methylmalonic Acid)
AB6MNQ6J6L (Succinic Acid)
MU72812GK0 (Creatine)
تواريخ الأحداث: Date Created: 20030507 Date Completed: 20030711 Latest Revision: 20190712
رمز التحديث: 20231215
DOI: 10.1016/s0306-4522(02)00978-8
PMID: 12732252
قاعدة البيانات: MEDLINE
الوصف
تدمد:0306-4522
DOI:10.1016/s0306-4522(02)00978-8