Highlighting the role of cognitive and brain reserve in the substance use disorder field

Author manuscriptBackground: Cognitive reserve (CR) refers to the ability of an individual to cope with brain pathology remaining free of cognitive symptoms. This protective factor has been related to compensatory and more efficient brain mechanisms involved in resisting brain damage. For its part, Brain reserve (BR) refers to individual differences in the structural properties of the brain which could also make us more resilient to suffer from neurodegenerative and mental diseases. Objective: This review summarizes how this construct, mainly mediated by educational level, occupational attainment, physical and mental activity, as well as successful social relationships, has gained scientific attention in the last years with regard to diseases, such as neurodegenerative diseases, stroke or traumatic brain injury. Nevertheless, although CR has been studied in a large number of disorders, few researches have addressed the role of this concept in drug addiction. Methods: We provide a selective overview of recent literature about the role of CR and BR in preventing substance use onset. Likewise, we will also discuss how variables involved in CR (healthy leisure, social support or job- related activities, among others) could be trained and included as complementary activities of substance use disorder treatments. Results: Evidence about this topic suggests a preventive role of CR and BR on drug use onset and when drug addiction is established, these factors led to less severe addiction-related problems, as well as better treatment outcomes. Conclusion: CR and BR are variables not taken yet into account in drug addiction. However, they could give us a valuable information about people at risk, as well as patient’s prognosis.This study was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO, Agencia Estatal de Investigación) cofounded by the European Research Development Fund -AEI/FEDER, UE- (PSI2015-73156-JIN to E.C.O.; PSI2017-82604R to L.J.S.) and from University of Malaga (Plan Propio 2017 – ‘Ayudas para proyectos dirigidos por jóvenes investigadores’, PPIT.UMA.B1.2017/38 to P.S.P.). Author D.L.G.M. holds a ‘FPU’ grant from the Spanish Ministry of Education, Culture and Sports (code: FPU13/04819). Author E.C.O. holds a ‘Jóvenes Investigadores’ grant (code: PSI2015-73156-JIN) from the Spanish Ministry of Economy and Competitiveness (Agencia Estatal de Investigación) co-funded by FEDER, UE. Author P.S.P. holds a ‘Juan de la Cierva-formación’ grant from the Spanish Ministry of Economy, Industry and Competitiveness (code: FJCI-2015-23925)

LPA1/3 receptor antagonist KI16425 as a novel treatment for the neurobehavioural effects of the ethanol

Aims. The lysophosphatidic acid (LPA) is an ubiquitous lysophospholipid that acts through G-protein coupled receptors (LPA1-6), and it is involved in the modulation of emotional and motivational behaviors. Recent literature suggests a relevant role of the LPA signaling system in alcoholism, specially through the LPA1 receptor. This work aims to elucidate whether systemic LPA1/3 receptor blockade with ki16425 would modulate ethanol effects on the brain and behavior. Methods. This study consisted of four experiments assessing the effect of intraperitoneal ki16425 administration (20 mg/kg) on ethanol-related behaviors. Male Wistar rats or mice (Swiss, C57BL/6J or hybrid C57BL/6J×129X1/SvJ background) were employed in various procedures: I) oral ethanol selfadministration; II) loss of righting reflex; III) ethanol-induced conditioned place preference (CPP) and IV) ethanol-withdrawal behavioral symptoms (by assessing nest building, physical signs and spatial working memory). Immunohistochemistry was carried out in order to evaluate basal neuronal activity (c-Fos) in the medial prefrontal cortex (mPFC) and in the hippocampus, as well as adult hippocampal neurogenesis (AHN) using proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) markers. Results. Systemic Ki16425 administration reduced oral self-administration of ethanol in previously trained rats. Likewise, ki16425 pretreatment in mice attenuated the sedation induced by ethanol, blocked ethanol rewarding effect in a CPP paradigm and reduced behavioral symptoms induced by ethanol withdrawal. Immunohistochemistry revealed a protective effect of ki16425 against ethanol actions on basal neuronal activity in the mPFC and on AHN. Conclusions. Our results suggest a potential usefulness of systemic LPA1/3 receptors antagonists as a novel treatment for alcohol-related disorders.Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tech

Aggravation of Chronic Stress Effects on Hippocampal Neurogenesis and Spatial Memory in LPA1 Receptor Knockout Mice

The lysophosphatidic acid LPA₁ receptor regulates plasticity and neurogenesis in the adult hippocampus. Here, we studied whether absence of the LPA₁ receptor modulated the detrimental effects of chronic stress on hippocampal neurogenesis and spatial memory.Male LPA₁-null (NULL) and wild-type (WT) mice were assigned to control or chronic stress conditions (21 days of restraint, 3 h/day). Immunohistochemistry for bromodeoxyuridine and endogenous markers was performed to examine hippocampal cell proliferation, survival, number and maturation of young neurons, hippocampal structure and apoptosis in the hippocampus. Corticosterone levels were measured in another a separate cohort of mice. Finally, the hole-board test assessed spatial reference and working memory. Under control conditions, NULL mice showed reduced cell proliferation, a defective population of young neurons, reduced hippocampal volume and moderate spatial memory deficits. However, the primary result is that chronic stress impaired hippocampal neurogenesis in NULLs more severely than in WT mice in terms of cell proliferation; apoptosis; the number and maturation of young neurons; and both the volume and neuronal density in the granular zone. Only stressed NULLs presented hypocortisolemia. Moreover, a dramatic deficit in spatial reference memory consolidation was observed in chronically stressed NULL mice, which was in contrast to the minor effect observed in stressed WT mice.These results reveal that the absence of the LPA₁ receptor aggravates the chronic stress-induced impairment to hippocampal neurogenesis and its dependent functions. Thus, modulation of the LPA₁ receptor pathway may be of interest with respect to the treatment of stress-induced hippocampal pathology

Journal Staff

We present the first measurements of the differential cross section d sigma/dp(T)(gamma) for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities vertical bar y(gamma)vertical bar < 1.0 and transverse momenta 30 < p(T)(gamma) < 200 GeV. The b-quark jets are required to have p(T)(jet) > 15 GeVand vertical bar y(jet)vertical bar < 1.5. The ratio of differential production cross sections for gamma + 2 b-jets to gamma + b-jet as a function of p(T)(gamma) is also presented. The results are based on the proton-antiproton collision data at root s = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron Collider. The measured cross sections and their ratios are compared to the next- to- leading order perturbative QCD calculations as well as predictions based on the k(T)- factorization approach and those from the sherpa and pythia Monte Carlo event generators

Double parton interactions in photon+3 jet events in ppbar collisions sqrt{s}=1.96 TeV

We have used a sample of photon+3 jets events collected by the D0 experiment with an integrated luminosity of about 1 fb^-1 to determine the fraction of events with double parton scattering (f_DP) in a single ppbar collision at sqrt{s}=1.96 TeV. The DP fraction and effective cross section (sigma_eff), a process-independent scale parameter related to the parton density inside the nucleon, are measured in three intervals of the second (ordered in pT) jet transverse momentum pT_jet2 within the range 15 < pT_jet2 < 30 GeV. In this range, f_DP varies between 0.23 < f_DP < 0.47, while sigma_eff has the average value sigma_eff_ave = 16.4 +- 0.3(stat) +- 2.3(syst) mb.Comment: 15 pages, 13 figure

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio

Measurement of the semileptonic charge asymmetry in B0 meson mixing with the D0 detector

We present a measurement of the semileptonic mixing asymmetry for B0 mesons, a^d_{sl}, using two independent decay channels: B0 -> mu+D-X, with D- -> K+pi-pi-; and B0 -> mu+D*-X, with D*- -> antiD0 pi-, antiD0 -> K+pi- (and charge conjugate processes). We use a data sample corresponding to 10.4 fb^{-1} of ppbar collisions at sqrt(s) = 1.96 TeV, collected with the D0 experiment at the Fermilab Tevatron collider. We extract the charge asymmetries in these two channels as a function of the visible proper decay length (VPDL) of the B0 meson, correct for detector-related asymmetries using data-driven methods, and account for dilution from charge-symmetric processes using Monte Carlo simulation. The final measurement combines four signal VPDL regions for each channel, yielding a^d_{sl} = [0.68 \pm 0.45 \text{(stat.)} \pm 0.14 \text{(syst.)}]%. This is the single most precise measurement of this parameter, with uncertainties smaller than the current world average of B factory measurements.Comment: Version includes minor textual changes following peer review by journal, most notably the updating of Ref. [21] to reflect the most recent publicatio

Search for B0→π0π0B^{0}\to \pi^{0}\pi^{0} Decay

We have searched for the charmless hadronic decay of B0 mesons into two neutral pions. Using 9.13fb^-1 taken at the Upsilon(4S) with the CLEO detector, we obtain an improved upper limit for the branching fraction BR(B0-->pi0pi0) < 5.7*10^-6 at the 90% confidence level.Comment: pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Dependence of the ttˉt\bar{t} production cross section on the transverse momentum of the top quark

We present a measurement of the differential cross section for $t\bar{t}$ events produced in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV as a function of the transverse momentum ($p_T$) of the top quark. The selected events contain a high-$p_T$ lepton ($\ell$), four or more jets, and a large imbalance in $p_T$, and correspond to 1 fb${}^{-1}$ of integrated luminosity recorded with the D0 detector. Each event must have at least one candidate for a $b$ jet. Objects in the event are associated through a constrained kinematic fit to the $t\bar{t}\to WbW\bar{b} \to \ell\nu b q\bar{q}'\bar{b}$ process. Results from next-to-leading-order perturbative QCD calculations agree with the measured differential cross section. Comparisons are also provided to predictions from Monte Carlo event generators using QCD calculations at different levels of precision.Comment: 8 pages, 6 figures, 4 tables, updated to reflect the published versio

Search for the Higgs boson in lepton, tau and jets final states

We present a search for the standard model Higgs boson in final states with an electron or muon and a hadronically decaying tau lepton in association with two or more jets using 9.7 fb^{-1} of Run II Fermilab Tevatron Collider data collected with the D0 detector. The analysis is sensitive to Higgs boson production via gluon fusion, associated vector boson production, and vector boson fusion, followed by the Higgs boson decay to tau lepton pairs or to W boson pairs. The ratios of 95% C.L. upper limits on the cross section times branching ratio to those predicted by the standard model are obtained for orthogonal subsamples that are enriched in either H -> tau tau decays or H -> WW decays, and for the combination of these subsample limits. The observed and expected limit ratios for the combined subsamples at a Higgs boson mass of 125 GeV are 11.3 and 9.0 respectively