Functional maturation of isolated neural progenitor cells from the adult rat hippocampus

Although neural progenitor cells (NPCs) may provide a source of new neurons to alleviate neural trauma, little is known about their electrical properties as they differentiate. We have previously shown that single NPCs from the adult rat hippocampus can be cloned in the presence of heparan sulphate chains purified from the hippocampus, and that these cells can be pushed into a proliferative phenotype with the mitogen FGF2 [Chipperfield, H., Bedi, K.S., Cool, S.M. & Nurcombe, V. (2002) Int. J. Dev. Biol., 46, 661-670]. In this study, the active and passive electrical properties of both undifferentiated and differentiated adult hippocampal NPCs, from 0 to 12 days in vitro as single-cell preparations, were investigated. Sparsely plated, undifferentiated NPCs had a resting membrane potential of approximate to -90 mV and were electrically inexcitable. In > 70%, ATP and benzoylbenzoyl-ATP evoked an inward current and membrane depolarization, whereas acetylcholine, noradrenaline, glutamate and GABA had no detectable effect. In Fura-2-loaded undifferentiated NPCs, ATP and benzoylbenzoyl-ATP evoked a transient increase in the intracellular free Ca2+ concentration, which was dependent on extracellular Ca2+ and was inhibited reversibly by pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), a P2 receptor antagonist. After differentiation, NPC-derived neurons became electrically excitable, expressing voltage-dependent TTX-sensitive Na+ channels, low- and high-voltage-activated Ca2+ channels and delayed-rectifier K+ channels. Differentiated cells also possessed functional glutamate, GABA, glycine and purinergic (P2X) receptors. Appearance of voltage-dependent and ligand-gated ion channels appears to be an important early step in the differentiation of NPCs

Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice

Although most of the proposed beneficial effects of fiber consumption have been attributed to viscous and gel-forming properties of soluble fiber, it is mainly insoluble cereal fiber and whole grains that are strongly associated with reduced diabetes risk in prospective cohort studies, indicating that other unknown mechanisms are likely to be involved. We performed a long-term study investigating potential protective effects of adding soluble guar fiber (10% w/w) vs. insoluble cereal fiber (10% w/w) to an isoenergetic and macronutrient matched high-fat diet in obesity-prone C57BL/6J mice. After 45 weeks, mice fed soluble vs. insoluble fiber showed both significantly increased body weight (41.8±3.0 vs. 33.6±1.5 g, P=.03) and elevated markers of insulin resistance. In mice fed soluble fiber, energy loss via the feces was significantly lower and colonic fermentation with production of short chain fatty acids (SCFA) was markedly increased. Gene expression analysis in white adipose tissue showed significantly increased levels of the fatty acid target G-protein coupled receptor-40 in soluble fiber-fed mice. Liver gene expression in the insoluble fiber group showed a pattern consistent with increased fatty acid oxidation. The present results show that soluble vs insoluble dietary fiber added to a high-fat, Western-style diet differently affected body weight and estimates of insulin sensitivity in obesity-prone mice. Soluble fiber intake with increased SCFA production significantly contributed to digested energy, thereby potentially outweighing the well known short-term beneficial effects of soluble fiber consumption

Energy landscape of relaxed amorphous silicon

We analyze the structure of the energy landscape of a well-relaxed 1000-atom model of amorphous silicon using the activation-relaxation technique (ART nouveau). Generating more than 40,000 events starting from a single minimum, we find that activated mechanisms are local in nature, that they are distributed uniformly throughout the model and that the activation energy is limited by the cost of breaking one bond, independently of the complexity of the mechanism. The overall shape of the activation-energy-barrier distribution is also insensitive to the exact details of the configuration, indicating that well-relaxed configurations see essentially the same environment. These results underscore the localized nature of relaxation in this material.Comment: 8 pages, 12 figure

Human Adult Neurogenesis: Evidence and Remaining Questions

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan

Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator

The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intraplantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and antiproBDNF pretreatment may alleviate the development of inflammatory pain.Cong Luo, Xiao-Lin Zhong, Fiona H. Zhou, Jia-yi Li, Pei Zhou, Jun-Mei Xu, Bo Song, Chang-Qi Li, Xin-Fu Zhou and Ru-Ping Da