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gene addiction

Marcos Ucha, Santiago M Coria, Adrián E Núñez, Raquel Santos-Toscano, David Roura-Martínez, Javier Fernández-Ruiz, Alejandro Higuera-Matas, Emilio Ambrosio
BACKGROUND: Addiction is a chronic disorder with a high risk of relapse. The neural mechanisms mediating addictions require protein synthesis, which could be relevant for the development of more effective treatments. The mTOR signaling pathway regulates protein synthesis processes that have recently been linked to the development of drug addiction. AIMS: To assess the effects of morphine self-administration and its subsequent extinction on the expression of several genes that act in this pathway, and on the levels of specific phosphoproteins (Akt, Gsk3α/β, mTOR, PDK1 and p70 S6 kinase) in the amygdala, nucleus accumbens, and the prefrontal cortex...
March 19, 2019: Journal of Psychopharmacology
Palaniraja Thandapani
Cancer is fueled by the aberrant activity of oncogenic and tumor suppressive pathways. Transcriptional dysregulation of these pathways play a major role both in the genesis and development of cancer. Dysregulation of transcriptional programs can be mediated by genetic and epigenetic alterations targeting both protein coding genes and non-coding regulatory elements like enhancers and super-enhancers. Super-enhancers, characterized as large clusters of enhancers in close proximity, have been identified as essential oncogenic drivers required for the maintenance of cancer cell identity...
March 15, 2019: Pharmacology & Therapeutics
Nikolay S Rovinskiy, Andrews A Agbleke, Olga N Chesnokova, N Patrick Higgins
Prokaryotes have an essential gene-gyrase-that catalyzes negative supercoiling of plasmid and chromosomal DNA. Negative supercoils influence DNA replication, transcription, homologous recombination, site-specific recombination, genetic transposition and sister chromosome segregation. Although E. coli and Salmonella Typhimurium are close relatives with a conserved set of essential genes, E. coli DNA has a supercoil density 15% higher than Salmonella , and E. coli cannot grow at the supercoil density maintained by wild type (WT) Salmonella ...
March 15, 2019: Microorganisms
Jared R Bagley, Karen K Szumlinski, Tod E Kippin
BACKGROUND AND PURPOSE: Addiction vulnerability involves complex gene X environment interactions leading to a pathological response to drugs. Identification of the genes mediating these interactions is an important step in understanding the underlying neurobiology and rarely have such analyses examined sex-specific influences. To dissect this interaction, we examined the impact of prenatal stress (PNS) on cocaine responsiveness in male and female mice of the BXD recombinant inbred panel...
March 15, 2019: British Journal of Pharmacology
J Gao, H-R Li, C Jin, J-H Jiang, J-Y Ding
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC...
March 12, 2019: Clinical & Translational Oncology
H Le-Niculescu, K Roseberry, D F Levey, J Rogers, K Kosary, S Prabha, T Jones, S Judd, M A McCormick, A R Wessel, A Williams, P L Phalen, F Mamdani, A Sequeira, S M Kurian, A B Niculescu
The biological fingerprint of environmental adversity may be key to understanding health and disease, as it encompasses the damage induced as well as the compensatory reactions of the organism. Metabolic and hormonal changes may be an informative but incomplete window into the underlying biology. We endeavored to identify objective blood gene expression biomarkers for psychological stress, a subjective sensation with biological roots. To quantify the stress perception at a particular moment in time, we used a simple visual analog scale for life stress in psychiatric patients, a high-risk group...
March 12, 2019: Molecular Psychiatry
Roberta Esposito, Daniela Esposito, Alfredo Ciccodicola, Valerio Costa
RET rearrangements as well as BRAF and RAS mutations drive differential pathway activation in papillary thyroid carcinomas, leading to different tumor phenotypes and prognoses. Although The Cancer Genome Atlas Consortium has identified tumor subgroups based on protein-coding gene signatures, neither expression of long non-coding RNAs (lncRNAs) nor their correlation with specific tumor-driving mutations and rearrangements have been systematically assessed. Here we reanalyzed our RNA-sequencing data using a de novo discovery approach to identify lncRNAs and define tumor subtype-specific signatures of annotated lncRNAs...
March 12, 2019: Cancer Research
Ana Marques, Tiphaine Vidal, Bruno Pereira, Eve Benchetrit, Julie Socha, Fanny Pineau, Alexis Elbaz, Fanny Artaud, Graziella Mangone, Hana You, Florence Cormier, Monique Galitstky, Elsa Pomies, Olivier Rascol, Pascal Derkinderen, Daniel Weintraub, Jean Christophe Corvol, Franck Durif
INTRODUCTION: The management of impulse control disorders (ICDs) in Parkinson's disease (PD) relies on their early identification, allowing adjustment of antiparkinsonian treatment before these manifestations lead to major social, financial or legal consequences. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) is an English-developed and -validated PD-specific rating scale constructed to support the rating of ICDs and related disorders and the assessment of changes in symptom severity over time, but it has not to date been validated in French...
March 4, 2019: Parkinsonism & related Disorders
Shravani Mitra, Suchandra Mukherjee, Sharmi Naha, Pinaki Chattopadhyay, Shanta Dutta, Sulagna Basu
Background: The bla NDM-1 (New Delhi Metallo-β-lactamase-1) gene has disseminated around the globe. NDM-1 producers are found to co-harbour resistance genes against many antimicrobials, including fluoroquinolones. The spread of large plasmids, carrying both bla NDM and plasmid-mediated fluoroquinolone resistance (PMQR) markers, is one of the main reasons for the failure of these essential antimicrobials. Methods: Enterobacteriaceae ( n  = 73) isolated from the blood of septicaemic neonates, admitted at a neonatal intensive care unit (NICU) in Kolkata, India, were identified followed by PFGE, antibiotic susceptibility testing and determination of MIC values for meropenem and ciprofloxacin...
2019: Antimicrobial Resistance and Infection Control
Niall Mortimer, Tatjana Ganster, Aet O'Leary, Sandy Popp, Florian Freudenberg, Andreas Reif, María Soler Artigas, Marta Ribasés, Josep Antoni Ramos-Quiroga, Klaus-Peter Lesch, Olga Rivero
Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum...
March 5, 2019: Neuropharmacology
Einat Peles, Orna Levran, Matthew Randesi, Jurg Ott, Mary Jeanne Kreek, Miriam Adelson
OBJECTIVES: We have previously shown associations between 4 genetic variants in opioid and stress-related genes (OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP) and prolonged abstinence from heroin without methadone maintenance treatment (MMT). We currently assessed the associations between these variants and MMT patients' characteristics. METHODS: A non-selective group of 351 patients who stayed at least 1 year in their first admission to MMT were genotyped and their characteristics and substance in urine on admission and after 1 year were studied...
March 4, 2019: Journal of Addiction Medicine
Ahmed El-Boraie, Taraneh Taghavi, Meghan J Chenoweth, Koya Fukunaga, Taisei Mushiroda, Michiaki Kubo, Caryn Lerman, Nicole L Nollen, Neal L Benowitz, Rachel F Tyndale
The nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is an index of CYP2A6 activity. CYP2A6 is responsible for nicotine's metabolic inactivation and variation in the NMR/CYP2A6 is associated with several smoking behaviors. Our aim was to integrate established alleles and novel genome-wide association studies (GWAS) signals to create a weighted genetic risk score (wGRS) for the CYP2A6 gene for European-ancestry populations. The wGRS was compared with a previous CYP2A6 gene scoring approach designed for an alternative phenotype (C2/N2; cotinine-d2/(nicotine-d2 + cotinine-d2))...
February 27, 2019: Addiction Biology
Giulia M Stella, Alessandra Corino, Giulia Berzero, Stefan Kolling, Andrea R Filippi, Silvia Benvenuti
The process of metastatic dissemination begins when malignant cells start to migrate and leave the primary mass. It is now known that neoplastic progression is associated with a combination of genetic and epigenetic events. Cancer is a genetic disease and this pathogenic concept is the basis for a new classification of tumours, based precisely on the presence of definite genetic lesions to which the clones are addicted. Regarding the scatter factor receptors MET and Recepteur d'Origin Nantais (RON), it is recognised that MET is an oncogene necessary for a narrow subset of tumours (MET-addicted) while it works as an adjuvant metastogene for many others...
February 26, 2019: Cancers
Gloria Pérez-Rubio, Elizabeth Córdoba-Lanús, Paula Cupertino, Francisco Cartujano-Barrera, Michael A Campos, Ramcés Falfán-Valencia
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in developed countries. Although cigarette smoking is the major risk factor, only 10-20% of smokers develop COPD. The extent of cigarette smoking (pack-years and smoking duration) accounts for only 15% of the variation in lung function, indicating that differences in susceptibility to COPD must exist. We provide an overview of the complexity of nicotine addiction and COPD, with special attention to the involvement of genetic factors...
2019: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Maria Vrettou, Kent W Nilsson, Catherine Tuvblad, Mattias Rehn, Cecilia Åslund, Anna-Karin Andershed, Åsa Wallén-Mackenzie, Henrik Andershed, Sheilagh Hodgins, Ingrid Nylander, Erika Comasco
The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors...
February 25, 2019: European Child & Adolescent Psychiatry
Saeideh Karimi-Haghighi, Leila Dargahi, Abbas Haghparast
Methamphetamine (METH) is a highly potent and addictive psychostimulant that is frequently abused worldwide. Although the biggest challenge to the efficient treatment of drug dependence is relapse, its mechanism is completely unclear. Plenty of evidence suggests that inflammation contributes to drug-induced reward especially in brain regions that are involved in the reward system, but there is no document about relapse. Cannabidiol (CBD) is a nonpsychoactive cannabinoid that has powerful anti-inflammatory and immunosuppressive properties...
February 22, 2019: Addiction Biology
Hai-Feng Lu, Wen Xiao, Si-Long Deng, Xiao-Ling Cheng, Hui-Ling Zheng, Jian-Guo Chen, Fang Wang
Cocaine is a strong central nervous system stimulant, which can induce drug addiction. Previous studies have reported that cocaine-induced autophagy is involved in neuroinflammation and cell death. However, the role of autophagy in psychomotor sensitivity to cocaine has not been explored. Here, we reported that D1 receptor -CaMKII-AMPK-FoxO3a signaling pathway was involved in acute cocaine application-induced autophagy in the nucleus accumbens (NAc) both in vitro and in vivo. Furthermore, we found that knockdown of the ATG5 gene in the NAc augmented behavioral response to cocaine, and induction of autophagy in the NAc with rapamycin attenuated cocaine-induced behavioral response, which was coincident with the alterations of dendritic spine density in neurons of NAc...
February 20, 2019: Addiction Biology
Gene-Jack Wang, Corinde E Wiers, Elena Shumay, Dardo Tomasi, Kai Yuan, Christopher T Wong, Jean Logan, Joanna S Fowler, Nora D Volkow
The response to drugs of abuse is affected by expectation, which is modulated in part by dopamine (DA), which encodes for a reward prediction error. Here we assessed the effect of expectation on methylphenidate (MP)-induced striatal DA changes in 23 participants with an active cocaine use disorder (CUD) and 23 healthy controls (HC) using [11 C]raclopride and PET both after placebo (PL) and after MP (0.5 mg/kg, i.v.). Brain dopamine D2 and D3 receptor availability (D2R: non-displaceable binding potential (BPND )) was measured under four conditions in randomized order: (1) expecting PL/receiving PL, (2) expecting PL/receiving MP, (3) expecting MP/receiving PL, and (4) expecting MP/receiving MP...
February 15, 2019: Translational Psychiatry
Taylor P LaRese, Bruce A Rheaume, Ron Abraham, Betty A Eipper, Richard E Mains
The nucleus accumbens plays a major role in the response of mammals to cocaine. In animal models and human studies, the addictive effects of cocaine and relapse probability have been shown to be greater in females. Sex-specific differential expression of key transcripts at baseline and after prolonged withdrawal could underlie these differences. To distinguish between these possibilities, gene expression was analyzed in four groups of mice (cycling females, ovariectomized females treated with estradiol or placebo, and males) 28 days after they had received seven daily injections of saline or cocaine...
February 1, 2019: Journal of the Endocrine Society
Gerard M Moloney, Wesley E P A van Oeffelen, Feargal J Ryan, Marcel van de Wouw, Caitlin Cowan, Marcus J Claesson, Harriet Schellekens, Timothy G Dinan, John F Cryan
Impulsivity is an important component of many psychiatric illnesses and has been associated with a number of psychiatric disorders such as bipolar disorder and attention deficit / hyperactivity disorder (ADHD). Exploring the different aspects of impulsive behaviour and assigning these to specific neurobiological pathways would advance our interpretation of disorders for which impulsivity is key. Pharmacological studies have implicated a number of neurotransmitters in impulsivity, which in turn have been shown to be affected by several genes in both rodent and human studies of impulsivity...
February 6, 2019: Behavioural Brain Research
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