دورية أكاديمية
أعرض في EDS

Enantiomers of 2-methylglutamate and 2-methylglutamine selectively impact mouse brain metabolism and behavior.

التفاصيل البيبلوغرافية
العنوان: Enantiomers of 2-methylglutamate and 2-methylglutamine selectively impact mouse brain metabolism and behavior.
المؤلفون: Wawro AM; Department of Pathology, Stanford University, Stanford, USA., Gajera CR; Department of Pathology, Stanford University, Stanford, USA., Baker SA; Department of Pathology, Stanford University, Stanford, USA., Leśniak RK; ChEM-H, Stanford University, Stanford, USA., Fischer CR; ChEM-H, Stanford University, Stanford, USA., Saw NL; Behavioral and Functional Neuroscience Laboratory, Stanford University, Stanford, USA., Shamloo M; Behavioral and Functional Neuroscience Laboratory, Stanford University, Stanford, USA.; Department of Neurosurgery, Stanford University, Stanford, USA., Montine TJ; Department of Pathology, Stanford University, Stanford, USA. tmontine@stanford.edu.
المصدر: Scientific reports [Sci Rep] 2021 Apr 14; Vol. 11 (1), pp. 8138. Date of Electronic Publication: 2021 Apr 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Brain/*metabolism , Glutamates/*administration & dosage , Glutamine/*administration & dosage , Synaptosomes/*metabolism, Animals ; Behavior, Animal/drug effects ; Chromatography, Liquid ; Dose-Response Relationship, Drug ; Female ; Glutamates/chemistry ; Glutamates/pharmacokinetics ; Glutamine/chemistry ; Glutamine/pharmacokinetics ; Male ; Mice ; Primary Cell Culture ; Stereoisomerism ; Tandem Mass Spectrometry ; gamma-Aminobutyric Acid/metabolism
مستخلص: Imbalance of excitatory and inhibitory neurotransmission is implicated in a wide range of psychiatric and neurologic disorders. Here we tested the hypothesis that insertion of a methyl group on the stereogenic alpha carbon of L-Glu or L-Gln would impact the γ-aminobutyric acid (GABA) shunt and the glutamate-glutamine cycle. (S)-2-methylglutamate, or (S)-2MeGlu, was efficiently transported into brain and synaptosomes where it was released by membrane depolarization in a manner equivalent to endogenous L-Glu. (R)-2MeGlu was transported less efficiently into brain and synaptosomes but was not released by membrane depolarization. Each enantiomer of 2MeGlu had limited activity across a panel of over 30 glutamate and GABA receptors. While neither enantiomer of 2MeGlu was metabolized along the GABA shunt, (S)-2MeGlu was selectively converted to (S)-2-methylglutamine, or (S)-2MeGln, which was subsequently slowly hydrolyzed back to (S)-2MeGlu in brain. rac-2MeGln was also transported into brain, with similar efficiency as (S)-2MeGlu. A battery of behavioral tests in young adult wild type mice showed safety with up to single 900 mg/kg dose of (R)-2MeGlu, (S)-2MeGlu, or rac-2MeGln, suppressed locomotor activity with single ≥ 100 mg/kg dose of (R)-2MeGlu or (S)-2MeGlu. No effect on anxiety or hippocampus-dependent learning was evident. Enantiomers of 2MeGlu and 2MeGln show promise as potential pharmacologic agents and imaging probes for cells that produce or transport L-Gln.
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المشرفين على المادة: 0 (Glutamates)
0RH81L854J (Glutamine)
470-51-9 (2-methylglutamic acid)
56-12-2 (gamma-Aminobutyric Acid)
تواريخ الأحداث: Date Created: 20210415 Date Completed: 20211115 Latest Revision: 20211115
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8047011
DOI: 10.1038/s41598-021-87569-1
PMID: 33854131
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-021-87569-1