PrPC Controls via Protein Kinase A the Direction of Synaptic Plasticity in the Immature Hippocampus

The cellular form of prion protein PrPC is highly expressed in the brain, where it can be converted into its abnormally folded isoform PrPSc to cause neurodegenerative diseases. Its predominant synaptic localization suggests a crucial role in synaptic signaling. Interestingly, PrPC is developmentally regulated and its high expression in the immature brain could be instrumental in regulating neurogenesis and cell proliferation. Here, PrPC-deficient (Prnp0/0) mice were used to assess whether the prion protein is involved in synaptic plasticity processes in the neonatal hippocampus. To this aim, calcium transients associated with giant depolarizing potentials, a hallmark of developmental networks, were transiently paired with mossy fiber activation in such a way that the two events were coincident. While this procedure caused long-term potentiation (LTP) in wild-type (WT) animals, it caused long-term depression (LTD) in Prnp0/0 mice. Induction of LTP was postsynaptic and required the activation of cAMP-dependent protein kinase A (PKA) signaling. The induction of LTD was presynaptic and relied on G-protein-coupled GluK1 receptor and protein lipase C. In addition, at emerging CA3-CA1 synapses in WT mice, but not in Prnp0/0 mice, pairing Schaffer collateral stimulation with depolarization of CA1 principal cells induced LTP, known to be PKA dependent. Postsynaptic infusion of a constitutively active isoform of PKA catalytic subunit C\u3b1 into CA1 and CA3 principal cells in the hippocampus of Prnp0/0 mice caused a persistent synaptic facilitation that was occluded by subsequent pairing. These data suggest that PrPC plays a crucial role in regulating via PKA synaptic plasticity in the developing hippocampus. \ua9 2013 the authors

Control of GABA Release at Mossy Fiber-CA3 Connections in the Developing Hippocampus

In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABAA-mediated postsynaptic currents (MF-GPSCs) exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABAB and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons), generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses

Features of the n-alkanes crystalline phase content in paraffin oil components and their deposits

High-molecular n-alkanes within high paraffin oils of remaining hard-to-recover reseives are studied. Oil paraffin hydrocarbons redistribution between oils and their heavy deposits in the downhole equipment is presented. The presence of n-alkanes in the oils asphaltenes and their deposits is shown. Asphaltenes, extracted from the oils and their asphaltene deposits, were investigated by high-temperature gas chromatography and differential scanning calorimetry, with the help of which it was succeeded to find the presence of high n-alkanes C40-C59 and higher ones in their composition judging by the crystallization temperature detected in the crystalline phase. The highest molecular weight n-alkanes, whose molecular mass distribution peak falls on C54-C58, were found In asphaltenes of oils with low paraffin wax content. The data on the crystalline phase content in oils, heavy oil deposits, asphaltenes samples, isolated from oils and heavy oil deposits, as well as on the crystallization temperature are presented. High-molecular oil paraffin hydrocarbons can serve as crystallization centers of the complex structural units in oil dispersion system and flocculate at the system unbalance at achieving the critical concentration. Paraffin hydrocarbons, containing in the asphaltenes, are able to migrate and accumulate within the oil heavy deposits under certain thermodynamic conditions, as evidenced by the different compositions of n-alkanes in the oil asphaltenes and in their deposits. Different kind of the heat capacity temperature dependences is stated for oils, the presence of paraffin wax crystal phase is revealed. Comparative analysis of differential scanning calorimetry data of samples indicates contradictory dependence of the crystallization temperature and crystalline phase content on the molecular mass distribution of n-alkanes, containing in their composition, and correlates with the molecular mass distribution of solid n-alkanes in the asphaltenes, that determines the differences in the structural organization of the dispersed phase in heavy oil deposits

Aquathermolysis of heavy oil using nano oxides of metals

© 2017 Elsevier B.V.The effect of suspended nanoparticles of magnetite and hematite on thermal decomposition of heavy oil at a temperature of 360 °C in a vapor medium at different system pressures is revealed. The preferential destruction reactions of macromolecular components of oil, which lead to the reduction of oil viscosity, are established. The effect of zinc and aluminum oxides as additives initiating cracking of hydrocarbon bonds is studied. The changes in structure of the component of the converted products, as compared to the original crude oil, are obtained. Conducting the process in the presence of additives at a pressure of 11 MPa led to the reduction of the aromaticity of the final products, increase in the yield of hydrocarbon oils and the formation of gaseous products. It is observed that the amount of asphalt-resinous substances is reduced as the result of their conversion in the presence of additives. Rheological curves of conversion products are obtained, based on them the peculiarities of viscosity-temperature characteristics change can be shown

Conversion of organic matter in the carbonaceous medium in the supercritical water

© 2017 Elsevier B.V. The work is based on the modeling of geothermal transformations of hydrocarbons in oil-bearing formations of deep horizons of the earth's crust - under abnormally high pressure, in the presence of aqueous fluid and carbonaceous substances. The pressure and temperature in the experiments are typical for water in the supercritical state. The regularities of the conversion of heavy oil in supercritical water and in the presence of finely dispersed caustobioliths and metal oxides were shown. Aquathermolysis in the presence of proton provides blockage of free radicals of high-molecular weight hydrocarbons and saturation of unsaturated hydrocarbons, produced by cracking reactions, and inhibiting of condensation reactions of aromatic macromolecules. The hydrogen protons also promote hydrogenation reactions in the crude oil. The regularities of changes of the component, structural-group, fractional and elemental compositions of heavy oil during the conversion under the above conditions were established, rheological characteristics of the initial crude oil and converted oil were studied as well. As a result of carrying out aquathermolysis in the supercritical water environment and in the presence of initiating additives, the high-molecular weight components of the initial crude oil were degraded with the formation of light distillate fractions, which were scarcely present in the initial crude oil. Thus, the conversion rate for various samples amounted to 18–29%. It resulted in the significant reduction in the viscosity of the converted oil, up to 96% compared to the initial crude oil

Developmental regulation of CB1-mediated spike-time dependent depression at immature mossy fiber-CA3 synapses

Early in postnatal life, mossy fibres (MF), the axons of granule cells in the dentate gyrus, release GABA which is depolarizing and excitatory. Synaptic currents undergo spike-time dependent long-term depression (STD-LTD) regardless of the temporal order of stimulation (pre versus post and viceversa). Here we show that at P3 but not at P21, STD-LTD, induced by negative pairing, is mediated by endocannabinoids mobilized from the postsynaptic cell during spiking-induced membrane depolarization. By diffusing backward, endocannabinoids activate cannabinoid type-1 (CB1) receptors probably expressed on MF. Thus, STD-LTD was prevented by CB1 receptor antagonists and was absent in CB1-KO mice. Consistent with these data, in situ hybridization experiments revealed detectable level of CB1 mRNA in the granule cell layer at P3 but not at P21. These results indicate that CB1 receptors are transiently expressed on immature MF terminals where they counteract the enhanced neuronal excitability induced by the excitatory action of GABA

On the structure of maximal solvable extensions and of Levi extensions of nilpotent algebras

We establish an improved upper estimate on dimension of any solvable algebra s with its nilradical isomorphic to a given nilpotent Lie algebra n. Next we consider Levi decomposable algebras with a given nilradical n and investigate restrictions on possible Levi factors originating from the structure of characteristic ideals of n. We present a new perspective on Turkowski's classification of Levi decomposable algebras up to dimension 9.Comment: 21 pages; major revision - one section added, another erased; author's version of the published pape

Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons

Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria

Bafilomycin A1 activates respiration of neuronal cells via uncoupling associated with flickering depolarization of mitochondria

Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca2+ and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12 (dPC12), dSH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in dPC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca2+ and ΔΨm. The response to Baf is regulated by cytosolic Ca2+ fluxes from the endoplasmic reticulum. Inhibition of permeability transition pore opening increases the depolarizing effect of Baf on the ΔΨm. Baf induces stochastic flickering of the ΔΨm with a period of 20 ± 10 s. Under conditions of suppressed ATP production by glycolysis, oxidative phosphorylation impaired by Baf does not provide cells with sufficient ATP levels. Cells treated with Baf become more susceptible to excitation with KCl. Such mitochondrial uncoupling may play a role in a number of (patho)physiological conditions induced by Baf