High-field 19.6T 27Al solid-state MAS NMR of in vitro aluminated brain tissue

The combination of (27)Al high-field solid-state NMR (19.6T) with rapid spinning speeds (17.8 kHz) is used to acquire (27)Al NMR spectra of total RNA human brain temporal lobe tissues exposed to 0.10 mM Al(3+) (as AlCl(3)) and of human retinal pigment epithelial cells (ARPE-19), grown in 0.10 mM AlCl(3). The spectra of these model systems show multiple Al(3+) binding sites, good signal/noise ratios and apparent chemical shift dispersions. A single broad peak (-3 to 11 ppm) is seen for the aluminated ARPE-19 cells, consistent with reported solution-state NMR chemical shifts of Al-transferrin. The aluminated brain tissue has a considerably different (27)Al MAS NMR spectrum. In addition to the transferrin-type resonance, additional peaks are seen. Tentative assignments include: -9 to -3 ppm, octahedral AlO(6) (phosphate and water); 9 ppm, condensed AlO(6) units (Al-O-Al bridges); 24 ppm, tetrahedral AlO(3)N and/or octahedral Al-carbonate; and 35 ppm, more N-substituted aluminum and /or tetrahedral AlO(4). Thus, brain tissue is susceptible to a broad range of coordination by aluminum. Furthermore, the moderate (27)Al C(Q) values (all less than 10 MHz) suggest future NMR studies may be performed at 9.4T and a spin rate of 20 kHz.     

Detection of d-serine in neural samples by saccharide enhanced chiral capillary electrophoresis

Highly fluorescent enantiomeric derivatives of d/l-serine from naphthalene-2,3-dicarboxaldehyde were resolved by hydroxypropyl-γ-cyclodextrin modified capillary electrophoresis using a saccharide as an enhancing chiral selector. Four saccharides, i.e. d-(+)-glucose, d-(−)-fructose, β-lactose, and sucrose were tested. Similar enhancing effects were observed. Coupled with laser induced fluorescence detection, this separation was applied to the determination of d-serine in neural samples including rat brain tissues, Aplysia ganglia, microdialysates from rat brain, and Aplysia individual neurons. High levels of d-serine were found in certain rat brain sections including hippocampus and striatum. d-Serine was also found to occur in Aplysia ganglia, but interestingly, it was not detected in single neurons isolated from Aplysia ganglia.     

Reducing inhomogeneity artifacts in functional MRI of human brain activation-thin sections vs gradient compensation

We evaluated two methods for correcting inhomogeneity-induced signal losses in magnetic resonance gradient-echo imaging that either use gradient compensation or simply acquire thin sections. The strategies were tested in the human brain in terms of achievable quality of T2*-weighted images at the level of the hippocampus and of functional activation maps of the visual cortex. Experiments were performed at 2.0 T and based on single-shot echo-planar imaging at 2. 0 x 2.0 mm(2) resolution, 4 mm section thickness, and 2.0 s temporal resolution. Gradient compensation involved a sequential 16-step variation of the refocusing lobe of the slice-selection gradient (TR/TE = 125/53 ms, flip angle 15 degrees ), whereas thin sections divided the 4-mm target plane into either four 1-mm or eight 0.5-mm interleaved multislice acquisitions (TR/TE = 2000/54 ms, flip angle 70 degrees ). Both approaches were capable of alleviating the inhomogeneity problem for structures in the base of the brain. When compared to standard 4-mm EPI, functional mapping in the visual cortex was partially compromised because of a lower signal-to-noise ratio of inhomogeneity-corrected images by either method. Relative to each other, consistently better results were obtained with the use of contiguous thin sections, in particular for a thickness of 1 mm. Multislice acquisitions of thin sections require minimal technical adjustments.     

Four correlates of complex behavioral networks: Differentiation,behavior, connectivity,and compartmentalization: Carving networks at their joints

Some of the most complex networks are those that (i) have been engineered under selective pressure (either economic or evolutionary), and (ii) are capable of eliciting network‐level behaviors. Some examples are nervous systems, ant colonies, electronic circuits and computer software. Here we provide evidence that many such selected, behavioral networks are similar in at least four respects. (1) Differentiation: Nodes of different types are used in a combinatorial fashion to build network structures through local connections, and networks accommodate more structure types via increasing the number of node types in the network (i.e., increasing differentiation), not via increasing the length of structures. (2) Behavior: Structures are themselves combined globally to implement behaviors, and networks accommodate a greater behavioral repertoire via increasing the number of lower‐level behavior types (including structures), not via increasing the length of behaviors. (3) Connectivity: In order for structures in behavioral networks to combine with other structures within a fixed behavior length, the network must maintain an invariant network diameter, and this is accomplished via increasing network connectivity in larger networks. (4) Compartmentalization: Finally, for reasons of economical wiring, behavioral networks become increasingly parcellated. Special attention is given to nervous systems and computer software, but data from a variety of other behavioral selected networks are also provided, including ant colonies, electronic circuits, web sites and businesses. A general framework is introduced illuminating why behavioral selected networks share these four correlates. Because the four above features appear to apply to computer software as well as to biological networks, computer software provides a useful framework for comprehending the large‐scale function and organization of biological networks. © 2005 Wiley Periodicals, Inc. Complexity 10: 13–40, 2005     

Biological efficacy of antisense oligonucleotides complementary to overlapping regions of the mRNA target

Phosphorothioate oligonucleotides complementary to target mRNA are stable in biological milieu and are capable of decreasing levels of this mRNA and the protein encoded by this mRNA (antisense knockdown). The results of our study are compared with the data published in the literature on the efficacy of three antisense 18—21-mer oligonucleotides, which are targeted to the start codon or nearby sequences of _2A-adrenoceptor mRNA, on receptor expression, and functions regulated by these receptors. The highest biological efficacy was shown by the oligonucleotide, which is complementary to the mRNA region and contains the largest number of unpaired bases in the theoretically calculated conformation corresponding to the free energy minimum. Targeting of both ends of the antisense on unpaired bases of the target also leads to the enhancement of its biological efficacy.     

脂质与健脑

脂质是人类的基本营养物质之一,是最重要的健脑营养素。本文介绍了脑的发育特点与脂代谢的关系;脂质的结构和分类,以及脂质的健脑益智作用。旨在正确认识脂类,科学摄取脂类,提高智力,促进素质教育。     

气相色谱/质谱联用测定大鼠脑部的神经甾体

应用气相色谱 质谱联用技术建立了大鼠脑部神经甾体的测定方法。游离型甾体和甾体硫酸酯分两步萃取。第一步用乙酸乙酯提取游离型甾体,第二步用氯仿/2 丁醇提取甾体硫酸酯,然后经固相萃取纯化。甾体硫酸酯进行溶剂解形成游离型甾体。游离型甾体和甾体硫酸酯分别经七氟丁酸酐衍生化后进行气相色谱 质谱分析。经初步研究雄性大鼠脑部游离型神经甾体孕烯醇酮(PREG)、黄体酮(PROG)、别孕烯醇酮(AP)和脱氢表雄酮(DHEA)的含量分别为（8.53±1.11） ng/g ,（ 7.01±2.60） ng/g ,（ 1.     

Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC–MS/MS

Previously compound I showed great anti-glioblastoma activity without toxicity in a mouse xenograft study. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed and validated to investigate the pharmacokinetics and brain distribution of compound I in mice. The protein precipitation method was applied to extract the compound from mouse plasma and brain homogenates, and it was then separated using a Kinetex C₁₈ column with a mobile phase consisting of acetonitrile–0.1% formic acid water (50:50, v/v). The analytes were detected with multiple reaction monitoring for the quantitative response of the compounds. The inter- and intra-day precisions were <8.29 and 3.85%, respectively, and the accuracy range was within ±7.33%. The method was successfully applied to evaluate the pharmacokinetics of compound I in mouse plasma and brain tissue. The peak concentration in plasma was achieved within 1 h. The apparent elimination half-life was 4.06 h. The peak concentration of compound I in brain tissue was 0.88 μg/g. The results indicated that compound I was rapidly distributed and could cross the blood–brain barrier. The pharmacokinetic profile summarized provides valuable information for the further investigation of compound I as a potential anti-glioblastoma agent.     

Smell and Stress Response in the Brain: Review of the Connection between Chemistry and Neuropharmacology

The stress response in the brain is not fully understood, although stress is one of the risk factors for developing mental disorders. On the other hand, the stimulation of the olfactory system can influence stress levels, and a certain smell has been empirically known to have a stress-suppressing effect, indeed. In this review, we first outline what stress is and previous studies on stress-responsive biomarkers (stress markers) in the brain. Subsequently, we confirm the olfactory system and review previous studies on the relationship between smell and stress response by species, such as humans, rats, and mice. Numerous studies demonstrated the stress-suppressing effects of aroma. There are also investigations showing the effects of odor that induce stress in experimental animals. In addition, we introduce recent studies on the effects of aroma of coffee beans and essential oils, such as lavender, cypress, α-pinene, and thyme linalool on the behavior and the expression of stress marker candidates in the brain. The transfer of volatile components into the brain is also discussed while using the results of thyme linalool as an example. These studies may provide a good opportunity to connect chemical research at the molecular level with neuropharmacological approaches in the future.