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gene addiction

Tellervo Korhonen, Anu Loukola, Jenni Hällfors, Veikko Salomaa, Jaakko Kaprio
Introduction: Brain derived neurotrophic factor (BDNF) is a growth factor in the central nervous system. There is evidence for the involvement of BDNF in addictions and mental disorders. We aimed to replicate the earlier reported association of a functional genetic variant of BDNF with smoking initiation (SI) using a large population-based sample, and to test whether the association is independent of depression. Methods: Our sample was drawn from the Finnish population-based FINRISK Surveys conducted in 1992, 1997, 2002 and 2007...
October 16, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Esther U Kim, Elena I Varlinskaya, Carol A Dannenhoffer, Linda P Spear
Alcohol use initiated early in adolescence is a major predictor for the development of alcohol use disorders. This risk may be increased when drinking is initiated around the time of puberty, given evidence of bidirectional relationships between alcohol and gonadal hormones. The current study examined the effects of adolescent intermittent ethanol exposure (AIE) on pubertal timing and expression of novelty-seeking and peer-directed behaviors as well as neural correlates of these behaviors. AIE did not affect pubertal timing or the later expression of novelty-seeking and peer-directed behaviors...
May 9, 2018: Alcohol
Changjiu Zhao, Stephen C Gammie
Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in the nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to non-parental adult mice to determine whether decreases in Nr1d1 expression in the NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social behaviors and mood-related behaviors...
October 16, 2018: European Journal of Neuroscience
Alan D Kaye, Elyse M Cornett, Shilpa S Patil, Sonja A Gennuso, Matthew M Colontonio, Dustin R Latimer, Aaron J Kaye, Richard D Urman, Nalini Vadivelu
There has been significant research to develop an ideal synthetic opioid. Opioids with variable properties possessing efficacy and with reduced side effects have been synthesized when compared to previously used agents. An opioid modulator is a drug that can produce both agonistic and antagonistic effects by binding to different opioid receptors and therefore cannot be classified as one or the other alone. These compounds can differ in their structures while still possessing opioid-mediated actions. This review will discuss TRV130 receptor modulators and other novel opioid receptor modulators, including Mitragyna "Kratom," Ignavine, Salvinorin-A, DPI-289, UFP-505, LP1, SKF-10,047, Cebranopadol, Naltrexone-14-O-sulfate, and Naloxegol...
June 2018: Best Practice & Research. Clinical Anaesthesiology
Shaunna L Clark, Blair N Costin, Robin F Chan, Alexander W Johnson, Linying Xie, Jessica L Jurmain, Gaurav Kumar, Andrey A Shabalin, Ashutosh K Pandey, Karolina A Aberg, Michael F Miles, Edwin van den Oord
BACKGROUND: Recent reviews have highlighted the potential use of blood-based methylation biomarkers as diagnostic and prognostic tools of current and future alcohol use and addiction. Due to the substantial overlap that often exists between methylation patterns across different tissues, including blood and brain, blood-based methylation may track methylation changes in brain, however, little work has explored the overlap in alcohol related methylation in these tissues. METHODS: To study the effects of alcohol on the brain methylome and identify possible biomarkers of these changes in blood, we performed a methylome-wide association study in brain and blood from 40 male DBA/2J mice that received either an acute ethanol or saline intraperitoneal injection...
October 15, 2018: Alcoholism, Clinical and Experimental Research
Dong Ho Woo, Jin Young Bae, Min-Ho Nam, Heeyoung An, Yeon Ha Ju, Joungha Won, Jae Hyouk Choi, Eun Mi Hwang, Kyung-Seok Han, Yong Chul Bae, C Justin Lee
Recently, μ-opioid receptor (MOR), one of the well-known Gi-protein coupled receptors (Gi-GPCR), was reported to be highly expressed in the hippocampal astrocytes. However, the role of astrocytic MOR has not been investigated. Here we report that activation of astrocytic MOR by [D-Ala2 ,N-MePhe4 ,Gly-ol]-enkephalin (DAMGO), a selective MOR agonist, causes a fast glutamate release using sniffer patch technique. We also found that the DAMGO-induced glutamate release was not observed in the astrocytes from MOR-deficient mice and MOR-short hairpin RNA (shRNA)-expressed astrocytes...
2018: Frontiers in Cellular Neuroscience
Lehao Wu, Weiyue Zhang, Xin Qiu, Chaoran Wang, Yanfang Liu, Zhiwei Wang, Yang Yu, Richard D Ye, Yan Zhang
Corydalis yanhusuo W. T. Wang ( C. yanhusuo ) has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of C. yanhusuo blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on C. yanhusuo , the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from C...
October 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Phyllis S Y Chong, Jianbiao Zhou, Jing-Yuan Chooi, Zit-Liang Chan, Sabrina Hui Min Toh, Tuan Zea Tan, Sheena Wee, Jayantha Gunaratne, Qi Zeng, Wee-Joo Chng
Aberrant activation of Wnt/β-catenin signaling pathway is essential for the development of AML; however, the mechanistic basis for this dysregulation is unclear. PRL-3 is an oncogenic phosphatase implicated in the development of LSCs. Here, we identified Leo1 as a direct and specific substrate of PRL-3. Serine-dephosphorylated form of Leo1 binds directly to β-catenin, promoting the nuclear accumulation of β-catenin and transactivation of TCF/LEF downstream target genes such as cyclin D1 and c-myc. Importantly, overexpression of PRL-3 in AML cells displayed enhanced sensitivity towards β-catenin inhibition in vitro and in vivo, suggesting that these cells are addicted to β-catenin signaling...
October 10, 2018: Oncogene
Rachel J Smith, Peter J Vento, Ying S Chao, Cameron H Good, Thomas C Jhou
The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic structure identified in 2009 that receives strong inputs from the lateral habenula and other sources, sends dense inhibitory projections to midbrain dopamine (DA) neurons, and plays increasingly recognized roles in aversive learning, addiction, and other motivated behaviors. In general, little is known about the genetic identity of these neurons. However, recent work has identified the transcription factor FoxP1 as enhanced in the mouse RMTg (Lahti et al...
October 9, 2018: Brain Structure & Function
Babita Madan, Nathan Harmston, Gahyathiri Nallan, Alex Montoya, Peter Faull, Enrico Petretto, David M Virshup
Activating mutations in the Wnt pathway drive a variety of cancers, but the specific targets and pathways activated by Wnt ligands are not fully understood. To bridge this knowledge gap, we performed a comprehensive time-course analysis of Wnt-dependent signaling pathways in an orthotopic model of Wnt-addicted pancreatic cancer, using a PORCN inhibitor currently in clinical trials, and validated key results in additional Wnt-addicted models. The temporal analysis of the drug-perturbed transcriptome demonstrated direct and indirect regulation of greater than 3,500 Wnt activated genes (23% of the transcriptome)...
October 9, 2018: Journal of Clinical Investigation
Jonghyuck Park, Joseph T Decker, Dominique R Smith, Brian J Cummings, Aileen J Anderson, Lonnie D Shea
Recently, many clinical trials have challenged the efficacy of current therapeutics for neuropathic pain after spinal cord injury (SCI) due to their life-threatening side-effects including addictions. Growing evidence suggests that persistent inflammatory responses after primary SCI lead to an imbalance between anti-inflammation and pro-inflammation, resulting in pathogenesis and maintenance of neuropathic pain. Conversely, a variety of data suggest that inflammation contributes to regeneration. Herein, we investigated long-term local immunomodulation using anti-inflammatory cytokine IL-10 or IL-4-encoding lentivirus delivered from multichannel bridges...
October 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Benoit Forget, Petra Scholze, Francina Langa, Carole Morel, Stephanie Pons, Sarah Mondoloni, Morgane Besson, Romain Durand-de Cuttoli, Audrey Hay, Ludovic Tricoire, Bertrand Lambolez, Alexandre Mourot, Philippe Faure, Uwe Maskos
Tobacco addiction is a chronic and relapsing disorder with an important genetic component that represents a major public health issue. Meta-analysis of large-scale human genome-wide association studies (GWASs) identified a frequent non-synonymous SNP in the gene coding for the α5 subunit of nicotinic acetylcholine receptors (α5SNP), which significantly increases the risk for tobacco dependence and delays smoking cessation. To dissect the neuronal mechanisms underlying the vulnerability to nicotine addiction in carriers of the α5SNP, we created rats expressing this polymorphism using zinc finger nuclease technology and evaluated their behavior under the intravenous nicotine-self-administration paradigm...
September 26, 2018: Current Biology: CB
Marek Schwendt, John Shallcross, Natalie A Hadad, Mark D Namba, Helmut Hiller, Lizhen Wu, Eric G Krause, Lori A Knackstedt
PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model of PTSD + CUD in order to identify the neurobiological changes underlying such comorbidity and screen potential medications for reducing cocaine seeking in the PTSD population. We utilized a predator scent stress model of PTSD, wherein rats received a single exposure to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible), intermediate, and resilient phenotypes were detected and were consistent with behavioral, corticosterone, and gene expression profiles 3 weeks post TMT...
October 5, 2018: Translational Psychiatry
Laura B Ferguson, Lingling Zhang, Shi Wang, Courtney Bridges, R Adron Harris, Igor Ponomarev
Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that act as transcription factors in response to endogenous lipid messengers. The fibrates and thiazolidinediones are synthetic PPAR agonists used clinically to treat dyslipidemia and Type 2 Diabetes Mellitus, respectively, but also improve symptoms of several other diseases. Transposable elements (TEs), repetitive sequences in mammalian genomes, are implicated in many of the same conditions for which PPAR agonists are therapeutic, including neurodegeneration, schizophrenia, and drug addiction...
2018: Frontiers in Molecular Neuroscience
Michael L Miller, Benjamin Chadwick, Dara L Dickstein, Immanuel Purushothaman, Gabor Egervari, Tanni Rahman, Chloe Tessereau, Patrick R Hof, Panos Roussos, Li Shen, Mark G Baxter, Yasmin L Hurd
Neuronal circuits within the prefrontal cortex (PFC) mediate higher cognitive functions and emotional regulation that are disrupted in psychiatric disorders. The PFC undergoes significant maturation during adolescence, a period when cannabis use in humans has been linked to subsequent vulnerability to psychiatric disorders such as addiction and schizophrenia. Here, we investigated in a rat model the effects of adolescent exposure to Δ9 -tetrahydrocannabinol (THC), a psychoactive component of cannabis, on the morphological architecture and transcriptional profile of layer III pyramidal neurons-using cell type- and layer-specific high-resolution microscopy, laser capture microdissection and next-generation RNA-sequencing...
October 3, 2018: Molecular Psychiatry
Kari Högstrand, Alf Grandien
Increased expression of the oncogene MYC is a common feature of many B cell malignancies, however MYC overexpression by itself is not sufficient for transformation, and additional genetic events are required, although the exact nature of these remains unknown. In patients and in transgenic mouse models, oncogenic transformation may occur in B cells at various differentiation stages interacting with complex microenvironment. B cell oncogenesis often occurs after prolonged periods of time, making it difficult to accurately identify the genetic events required for transformation...
October 3, 2018: European Journal of Immunology
Yangyang Cao, Haoqing Yang, Luyuan Jin, Juan Du, Zhipeng Fan
Bone marrow mesenchymal stem cells (BMSCs) nowadays are regarded as promising candidates in cell-based therapy for the regeneration of damaged bone tissues that are either incurable or intractable due to the insufficiency of current therapies. Recent studies suggest that BMSCs differentiate into osteoblasts, and that this differentiation is regulated by some specific patterns of epigenetic modifications, such as DNA methylation. However, the potential role of DNA methylation modification in BMSC osteogenic differentiation is unclear...
2018: Stem Cells International
Jinkai Sui, Chunkai Wang, Xiaofeng Liu, Ning Fang, Yanhua Liu, Wenjing Wang, Ning Yan, Huai-Bao Zhang, Yongmei Du, Xinmin Liu, Tiegang Lu, Zhongfeng Zhang, Hongbo Zhang
Cembranoids are a group of natural diterpenoid compounds with pharmaceutical potentials, and the cembratriene-diols produced by Nicotiana (tobacco) species display activities in anti-nicotine addiction and neuron protection. Although the enzymes catalyzing cembratriene-diols' formation in tobacco have been investigated, the regulatory mechanism underlying this physiological process remains unknown. This study has investigated the roles of phytohormone jasmonic acid (JA) in regulating cembratriene-diol formation in N...
September 30, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yang Fan, Zhao Ya-E, Wei Ji-Dong, Lu Yu-Fan, Zhang Ying, Song Ya-Lun, Ma Meng-Yu, Zhang Rui-Ling
Alcohol dependence was a global public health problem, yet the mechanisms of alcohol dependence has incompletely understood. The traditional view consider ethanol alter various neurotransmitters and their receptors in brain and develop the addiction. However, an increasing experimental evidences suggest that gut microbiota also influence brain functions via gut-to-brain interactions, and may therefore induce the development of alcohol use disorders. In this study, a rat model of alcohol dependence and withdrawal was employed, the gut microbiota composition was analyzed by high-throughput 16S rRNA gene sequencing, and the metagenome function was predicted by PICRUSt software...
September 20, 2018: Journal of Microbiology and Biotechnology
Kyle L Ploense, Xiang Li, Danay Baker-Andresen, Amanda E Carr, Nick Woodward, Jared Bagley, Karen K Szumlinski, Timothy W Bredy, Tod E Kippin
Repeated cocaine administration induces many long-term structural and molecular changes in the dorsal medial prefrontal cortex (dmPFC) and are known to underlie aspects of cocaine-seeking behavior. DNA methylation is a key long-lasting epigenetic determinant of gene expression and is implicated in neuroplasticity, however, the extent to which this epigenetic modification is involved in the neuroplasticity associated with drug addiction has received limited attention. Here, we examine the relation between DNA methylation and gene expression within the dorsal medial prefrontal cortex (dmPFC) following limited cocaine self-administration (1 h/day), prolonged cocaine self-administration (6 h/day), and saline self-administration (1 h/day)...
September 27, 2018: Neuropharmacology
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