MRS定量检测活体γ-氨基丁酸浓度的研究现状

γ-氨基丁酸（GABA）是一种重要的脑代谢物, 磁共振频谱(MRS)技术可以非介入检测活体脑代谢物浓度. 但使用MRS定量检测活体GABA还是会遇到很多困难. 随着谱编辑技术的发展和频谱分析软件的出现, 已提出了很多方法用于定量检测活体GABA浓度. 本文简述了GABA的理论背景, 然后介绍了国内外MRS定量检测活体γ 氨基丁酸浓度的研究现状, 最后分析了MRS定量检测γ 氨基丁酸浓度的方向.      

A simple synthesis of γ-aminoacids

The addition of dianions of carboxylic acids to bromoacetonitrile, leads, in good yields, to the corresponding γ-cyanoacids that give γ-aminoacids on hydrogenation. This two-step methodology improves the results previously described.     

New building blocks for peptide and depsipeptide synthesis: hexafluoroacetone protected l-homoisoserine and d,l-homoisocysteine derivatives

Efficient syntheses of l-homoisoserine and d,l-homoisocysteine derivatives starting from l-malic and d,l-thiomalic acid using hexafluoroacetone as protecting and activating agent are described. The new compounds are interesting building blocks for the preparation of non-natural peptides and depsipeptides as well as for the construction of new GABA derivatives.     

The Effects of Glutamate and GABA (Gamma-Amino-Butyric-Acid) on Spontaneous Acetylcholine Release at the Neuromuscular Junction in Xenopus Laevis Embryo Cell Cultures

The miniature endplate currents (MEPC's) were recorded at the neuromuscular junction of Xenopus laevis embryo neuron-muscle co-cultured cells. These MEPC's were due to the spontaneous release of acetylcholine from the nerve terminal. After perfusion with glutamate (10 μmol/L), both frequency and amplitude of the MEPC's increased. After washing away of glutamate, this effect persisted. We named this phenomena "Long-Term Facilitation".GABA (20 μmol/L) on the other hand had an inhibitory effect on both frequency and amplitude of the MEPC's. After washing away of GABA, the MEPC frequency and amplitude increased. We named this effect "Post-Potentiation". Local perfusion experiments furthermore indicated that the effect of glutamate was restricted to the neuromuscular junction, the effect of GABA was restricted to the soma.     

γ-Fluorophenyl-GABA derivatives from fluorobenzonitriles in high diastereomeric and enantiomeric excess

An enantioselective synthesis of α-fluoroaryl homoallylic amines in 52-71% yields and 76-93% enantioselectivities has been achieved via the allylboration of the corresponding fluorinated N-aluminobenzaldimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by alkaline hydrogen peroxide workup. Crotylboration of these aluminobenzaldimines with potassium B-methoxy B-E- or -Z-crotyldiisopinocampheylborinate provided the corresponding β-anti- or -syn-methyl α-fluoroarylhomoallylamines, respectively in high de and ee. Similarly, alkoxyallylboration with lithium B-methoxy B-γ-OMEMallyldiisopinocampheylborinate provided the corresponding β-syn-alkoxyhomoallylamines in excellent de and ee. Representatives of these amino alkenes were converted to the corresponding optically active N-Boc-protected fluorinated amino alcohols via hydroboration-oxidation. Further chromium-mediated oxidation provided N-Boc-protected γ-fluorophenyl-γ-aminobutyric acids, which upon deprotection provided the corresponding γ-lactams.     

Synthesis of imidazole phosphinic acids as I4AA analogues

The GABA_C receptor has been identified as a potentially attractive target involved in a number of eye diseases. TPMPA is the best antagonist reported so far. The synthesis of two new pharmacophores based on imidazole phosphinic acid core structure will be presented.     

人脑GABA测量在临床3 T磁共振成像系统上的实现

γ-氨基丁酸(γ-Aminobutyric Acid,GABA)是人脑中枢神经系统中一种重要的抑制性神经递质,对神经活动的调节起着主导作用.由于人脑GABA固有含量低以及与其他代谢物谱峰的重叠,在临床用磁共振成像系统中使用点分辨波谱(PRESS)序列或受激回波采集模式(STEAM)序列难以直接检测到GABA δ 3.01信号. 该文报道了MEGA-PRESS脉冲序列在临床用3 T磁共振成像系统上的实现,采用J差分谱编辑技术实现了对GABA的检测. 水模实验和人脑在体实验显示,MEGA-PRESS序列对GABA δ 3.01信号具有较好的检测效果.     

在体检测γ-氨基丁酸的MEGA-PRESS序列优化设计

γ-氨基丁酸（γ-aminobutyric acid,GABA）含量异常会引发一系列大脑疾病,因此在体检测人脑GABA含量成为一种十分必要的医疗技术.本文基于GABA检测常用的谱编辑方法MEGA-PRESS,引入性能更好的SLR脉冲代替常用的高斯脉冲,并使用单频带和双频带结合的方法激发特定频率的物质,在联影（United Imaging Healthcare,UIH）的uMR780磁共振系统上实现了一种优化的MEGA-PRESS序列.结果表明：SLR脉冲可以减少大分子（macromolecule,MM）信号对GABA信号的干扰;单频带和双频带结合可以更好地抑制残余水信号对GABA^*信号的影响.水模实验和人体实验结果均证实优化的MEGA-PRESS序列可以更好地实现GABA^*含量在体检测.     

Sleep and Its Modulation by Drugs That Affect GABAA Receptor Function

Most sleeping pills are made up of chemical compounds that are ligands for allosteric modulatory binding sites on the GABA_A receptor. Polysomnographic studies demonstrate that these hypnotics effectively increase the ability to fall and to stay asleep, but disrupt the physiological sleep profile (typical electroencephalograms (EEG) for the awake state and the different states of sleep are shown). Hence, there is an urgent need for sleep-promoting substances with a different mechanism of action. GABA analogues are one class of promising molecules.     

Effective Components and Molecular Mechanism of Agarwood Essential Oil Inhalation and the Sedative and Hypnotic Effects Based on GC-MS-Qtof and Molecular Docking

Agarwood has been used for the administration of hypnotic therapy. Its aromatic scent induces a relaxed state. However, its aromatic constituents and the underlying molecular effect are still unclear. This study aims to determine the active substance and molecular mechanism of the hypnotic effect of agarwood essential oil (AEO) incense inhalation in insomniac mice. Insomnia models were induced by para-chlorophenylalanine (PCPA, 300 mg/kg) in mice. The sleep-promoting effect was evaluated. Neurotransmitter levels and its receptor were detected to explore the molecular mechanism. The effective components were analyzed by GC-Q/TOF-MS of AEO. The binding mechanisms of the core compounds and core targets were verified by molecular docking. These results showed that AEO inhalation could significantly shorten sleep latency and prolong sleep time, inhibit autonomous activity and exert good sedative and sleep-promoting effects. A mechanistic study showed that AEO inhalation increased the levels of γ-aminobutyric acid (GABA_A), the GABA_A/glutamic acid (Glu) ratio, 5-hydroxytryptamine (5-HT) and adenosine (AD), upregulated the expression levels of GluR1, VGluT1 and 5-HT1A and downregulated 5-HT2A levels. Component analysis showed that the most abundant medicinal compounds were eremophilanes, cadinanes and eudesmanes. Moreover, the docking results showed that the core components stably bind to various receptors. The study demonstrated the bioactive constituents and mechanisms of AEO in its sedative and hypnotic effects and its multicomponent, multitarget and multipathway treatment characteristics in PCPA-induced insomniac mice. These results provide theoretical evidence for insomnia treatment and pharmaceutical product development with AEO.