Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain

The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.     

Comment on "Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain"

Manganas et al. (Reports, 9 November 2007, p. 980) used nuclear magnetic resonance spectroscopy to identify a biomarker of neural progenitor cells. However, their analysis relies on spectral processing methods that are known to be problematic. Absent detection using alternate methods of spectrum analysis or controls to quantify the false discovery rate, their conclusions may be premature.     

Magnesium pemoline: enhancement of brain RNA polymerases

The stimulation by magnesium pemoline of systems that synthesize brain nucleic acid was studied in vivo and in vitro. There are differential effects between true RNA polymerase and pseudo-RNA polymerase. The selective stimulation of true RNA polymerase by magnesium pemoline was not observed with stimulants of the central nervous system and psychotropic agents.     

Magnesium pemoline: failure to affect in vivo synthesis of brain RNA

The effect of magnesium pemoline on the synthesis of brain RNA in vivo was studied. No significant effect either on the concentration of RNA or on the uptake of H(3)-uridine into RNA was detected.     

Drugs in the brain

In our studies on the entry of drugs into the central nervous system we have found the technique of autoradiography combined with radioassay to be a valuable research tool. It has disclosed such unsuspected phenomena as the dual routes of entry into the brain of acetazolamide. Although many factors controlling drug entry remain to be studied, we propose certain general conclusions. 1) The anatomical boundaries of brain are clearly reflected by the penetration and accumulation of all compounds we have studied-a finding that confirms the original proposition that whole-brain homogenates are inadequate for the study of drug and brain relationships. 2) Circulation, expressed as egional blood flow or volume of capillary blood, was seldom decisive in nfluencing entry or accumulation of exogenous substances in the brain. To date, the only compounds demonstrated to be circulation-dependent are trifluoroiodomethane and thiopental. Both are extremely fat-soluble. Tissue binding appears to be an additional factor in the case of thiopental. 3) Penetration is retarded by myelin. All substances we have studied have shown a relatively slower rate of entry into this tissue. In immature brain, before myelinization has taken lace, the primordial white matter is readily penetrated. We have suggested that entry into mature white matter is retarded by the lamellated membranes of the myelin sheath, which should be regarded, therefore, as a component of the blood-brain barrier. The small interstitial space indicated by the limited entry of sulfate ion is an additional hindrance to dispersal of exogenous substances into brain parenchyma. The blood-brain barrier is a complex anatomical, physiological, and biochemical phenomenon, and no unitary hypothesis is adequate to embrace all the observed events. 4) Accumulation of a drug in the brain implies some form of binding or interaction between drug and tissue. Findings on injection of phenobarbital, thiopental, or diphenylhydantoin illustrate such an accumulation. These binding interactions may be nonspecific, as is probable in the case of drugs bound to plasma protein. However, a more fundamental significance is suggested when a drug is found to bind, react with, or accumulate in, a specific anatomical structure of the brain. We have made reference to this possibility in connection with the localization of isonicotinic acid hydrazide or its metabolites in the hippocampus (46), and we have also reported the striking accumulation of acetazolamide in hippocampus, caudate nucleus, and hypothalamus. Although the binding process is poorly understood, further investigation of these phenomena should lead to a clearer understanding of regional variations in brain chemistry. While one should not assume that the demonstration of a focal concentration of a drug implies site of action, correlation between pharmacological action, electrophysiological events, biochemical changes, and temporal and regional drug concentrations may indeed exist (47).     

RNAi技术对人脑微血管内皮细胞ANXA2基因表达水平的影响

目的 研究RNAi技术对人脑微血管内皮细胞(Human brain microvascular cells,HBMEC)ANXA2基因表达水平的影响.方法 将化学合成三对siRNA采用riboFECTTM CP转染试剂介导法转染HBMEC,应用荧光定量PCR法检测RNA干扰后ANXA2 mRNA表达量,得出抑制率.应用Westem-blot检测RNA干扰后对ANXA2蛋白表达的影响.结果 成功将siRNA转染HBMEC,荧光定量PCR吉果显示,在转染24 h后,各干扰组与阴性组比较ANXA2基因表达量明显下调(P＜0.01),Western-blot显示siRNA-ANXA2-2、siRNA-ANXA2-3转染前后ANXA2蛋白的表达水平明显受到抑制.结论 合成的ANXA2 siRNA能有效抑制ANXA2蛋白的表达、降低ANXA2 mRNA水平,对ANXA2有高效和特异的沉默作用,以ANXA2为靶点的RNA干扰技术可望成为鉴定HBMEC有关EV71膜受体的新策略.     

Evolution in the social brain

The evolution of unusually large brains in some groups of animals, notably primates, has long been a puzzle. Although early explanations tended to emphasize the brain's role in sensory or technical competence (foraging skills, innovations, and way-finding), the balance of evidence now clearly favors the suggestion that it was the computational demands of living in large, complex societies that selected for large brains. However, recent analyses suggest that it may have been the particular demands of the more intense forms of pairbonding that was the critical factor that triggered this evolutionary development. This may explain why primate sociality seems to be so different from that found in most other birds and mammals: Primate sociality is based on bonded relationships of a kind that are found only in pairbonds in other taxa.     

Endocannabinoid signaling in the brain

The primary psychoactive ingredient in cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), affects the brain mainly by activating a specific receptor (CB1). CB1 is expressed at high levels in many brain regions, and several endogenous brain lipids have been identified as CB1 ligands. In contrast to classical neurotransmitters, endogenous cannabinoids can function as retrograde synaptic messengers: They are released from postsynaptic neurons and travel backward across synapses, activating CB1 on presynaptic axons and suppressing neurotransmitter release. Cannabinoids may affect memory, cognition, and pain perception by means of this cellular mechanism.     

RNA as an RNA polymerase: net elongation of an RNA primer catalyzed by the Tetrahymena ribozyme

A catalytic RNA (ribozyme) derived from an intervening sequence (IVS) RNA of Tetrahymena thermophila will catalyze an RNA polymerization reaction in which pentacytidylic acid (C5) is extended by the successive addition of mononucleotides derived from a guanylyl-(3',5')-nucleotide (GpN). Cytidines or uridines are added to C5 to generate chain lengths of 10 to 11 nucleotides, with longer products being generated at greatly reduced efficiency. The reaction is analogous to that catalyzed by a replicase with C5 acting as the primer, GpNs as the nucleoside triphosphates, and a sequence in the ribozyme providing a template. The demonstration that an RNA enzyme can catalyze net elongation of an RNA primer supports theories of prebiotic RNA self-replication.     

松材线虫RNA聚合酶基因的RNA干扰研究

克隆了松材线虫(Bursaphelenchus xylophilus)RNA聚合酶基因片段,构建大量表达松材线虫RNA聚合酶基因片段的特异双链RNA(dsRNA)表达载体,并用表达的双链RNA(dsRNA)对松材线虫进行了RNA干扰实验。结果表明,松材线虫浸泡在20℃的RNA聚合酶基因双链RNA(dsRNA)溶液中干扰24 h后再培养12 d,其繁殖倍数为73.2;对照处理的繁殖倍数为322.8,两者的繁殖倍数相差4.4倍;松材线虫浸泡在4℃的RNA聚合酶基因双链RNA(dsRNA)溶液中干扰24 h后再培养12 d,其繁殖倍数为120.8。RNA聚合酶基因的双链RNA(dsRNA)浸泡明显的抑制了松材线虫的繁殖;并且发现利用浸泡法对线虫进行干扰试验,双链RNA(dsRNA)20℃浸泡的干扰效果要好于前人报道4℃浸泡的干扰效果。     

Viral RNA subunits in cells transformed by RNA tumor viruses

Single-stranded 35S and 20S viral RNA species are synthesized in virus-producing mouse and rat cells transformed by the murine sarcoma virus. A transformed hamster cell line that does not produce virus synthesizes 35S, but not 20S viral RNA.     

Communication in neuronal networks

Brains perform with remarkable efficiency, are capable of prodigious computation, and are marvels of communication. We are beginning to understand some of the geometric, biophysical, and energy constraints that have governed the evolution of cortical networks. To operate efficiently within these constraints, nature has optimized the structure and function of cortical networks with design principles similar to those used in electronic networks. The brain also exploits the adaptability of biological systems to reconfigure in response to changing needs.     

Quantitative mass spectrometry identifies insulin signaling targets in C. elegans

DAF-2, an insulin receptor-like protein, regulates metabolism, development, and aging in Caenorhabditis elegans. In a quantitative proteomic study, we identified 86 proteins that were more or less abundant in long-lived daf-2 mutant worms than in wild-type worms. Genetic studies on a subset of these proteins indicated that they act in one or more processes regulated by DAF-2, including entry into the dauer developmental stage and aging. In particular, we discovered a compensatory mechanism activated in response to reduced DAF-2 signaling, which involves the protein phosphatase calcineurin.     

Cloning of breakpoints of a chromosome translocation identifies the AN2 locus

Chromosome translocations involving 11p13 have been associated with familial aniridia in two kindreds highlighting the chromosomal localization of the AN2 locus. This locus is also part of the WAGR complex (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation). In one kindred, the translocation is associated with a deletion, and probes for this region were used to identify and clone the breakpoints of the translocation in the second kindred. Comparison of phage restriction maps exclude the presence of any sizable deletion in this case. Sequences at the chromosome 11 breakpoint are conserved in multiple species, suggesting that the translocation falls within the AN2 gene.