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https://www.readbyqxmd.com/read/28938182/the-genetic-epidemiology-of-substance-use-disorder-a-review
#1
REVIEW
Elizabeth C Prom-Wormley, Jane Ebejer, Danielle M Dick, M Scott Bowers
BACKGROUND: Substance use disorder (SUD) remains a significant public health issue. A greater understanding of how genes and environment interact to regulate phenotypes comprising SUD will facilitate directed treatments and prevention. METHODS: The literature studying the neurobiological correlates of SUD with a focus on the genetic and environmental influences underlying these mechanisms was reviewed. Results from twin/family, human genetic association, gene-environment interaction, epigenetic literature, phenome-wide association studies are summarized for alcohol, nicotine, cannabinoids, cocaine, and opioids...
August 1, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28937602/licochalcone-a-prevents-the-loss-of-dopaminergic-neurons-by-inhibiting-microglial-activation-in-lipopolysaccharide-lps-induced-parkinson-s-disease-models
#2
Bingxu Huang, Juxiong Liu, Chen Ju, Dongxue Yang, Guangxin Chen, Shiyao Xu, Yalong Zeng, Xuan Yan, Wei Wang, Dianfeng Liu, Shoupeng Fu
The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28937035/effects-of-pinealectomy-and-gonadectomy-on-olfactory-bulb-dopaminergic-neurons-in-rats
#3
Yan Li, Jian Zhu, Ying Wang, Lei Guo, Lei Li, Dong Wang
BACKGROUND: Olfactory disorder is an early manifestation of Parkinson's disease (PD), likely to be associated with abnormalities of the dopaminergic neurons in the olfactory bulb (OB); however, the causes of olfactory disorder in PD are not entirely clear. Some studies showed that melatonin (MT) and androgens (mainly testosterone, T) might participate in the pathogenesis of PD. The research aimed to investigate effects of MT or T deficiency on OB dopaminergic neurons in rats. METHODS: One hundred and twenty normal male Wistar rats were randomly divided into the control, sham operation pinealectomy (PX), sham operation gonadectomy (GDX), PX, GDX, and PX + GDX groups...
October 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28936820/-efficacy-of-low-dose-aripiprazole-to-treat-clozapine-associated-tardive-dystonia-in-a-patient-with-schizophrenia
#4
Lyang Huh, Bong Ju Lee
Tardive dystonia (TDt) is a debilitating side effect of long-term antipsychotic treatment. Even though TDt is associated with increased psychiatric morbidity, mortality, and severely decreased quality of life, there are no treatment modalities for TDt. Clozapine has been used as a treatment option for TDt in patients with schizophrenia. Interestingly, several recent case reports have indicated that it can enhance or induce TDt. We report a case of clozapine-associated TDt that was treated with low-dose aripiprazole (0...
2017: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
https://www.readbyqxmd.com/read/28935882/clinical-and-radiological-diversity-in-genetically-confirmed-primary-familial-brain-calcification
#5
Shingo Koyama, Hidenori Sato, Ryota Kobayashi, Shinobu Kawakatsu, Masayuki Kurimura, Manabu Wada, Toru Kawanami, Takeo Kato
Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935766/serotonin-2b-receptors-in-mesoaccumbens-dopamine-pathway-regulate-cocaine-responses
#6
Stéphane Doly, Emily Quentin, Raphaël Eddine, Stefania Tolu, Sebastian P Fernandez, Jesus Bertran-Gonzalez, Emmanuel Valjent, Arnauld Belmer, Xavier Viñals, Jacques Callebert, Philippe Faure, Frank J Meye, Denis Hervé, Patricia Robledo, Manuel Mameli, Jean-Marie Launay, Rafael Maldonado, Luc Maroteaux
Addiction is a maladaptive pattern of behavior following repeated use of reinforcing drugs in predisposed individuals, and leading to lifelong changes. A common substrate of these changes lies in alterations of neurons releasing dopamine in the ventral and dorsal territories of the striatum. The serotonin 5-HT2B receptor has been involved in various behaviors including impulsivity, response to antidepressants and to psychostimulants pointing toward putative interactions with the dopamine system. Despite these findings, it remains unknown whether 5-HT2B receptors directly modulate dopaminergic activity and the possible mechanisms involved...
September 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28935656/the-effect-of-chronic-treatment-with-lurasidone-on-rat-liver-cytochrome-p450-expression-and-activity-in-the-chronic-mild-stress-cms-model-of-depression
#7
Marta Kot, Anna Haduch, Mariusz Papp, Władysława Anna Daniel
Recent studies indicated an important role of the monoaminergic nervous systems (dopaminergic, noradrenergic and serotonergic systems) and stress in the regulation of cytochrome P450 (CYP) expression and activity in the liver. The aim of our present research was to determine the effect of the novel atypical neuroleptic drug with antidepressant properties lurasidone, on the expression (mRNA and protein level) and activity of liver CYP isoforms involved in the metabolism of drugs and endogenous steroids, in the chronic mild stress (CMS) model of depression...
September 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#8
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933786/pink1-interacts-with-%C3%AE-synuclein-and-abrogates-%C3%AE-synuclein-induced-neurotoxicity-by-activating-autophagy
#9
Jia Liu, Xue Wang, Yongquan Lu, Chunli Duan, Ge Gao, Lingling Lu, Hui Yang
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. α-synuclein (α-syn) and PTEN-induced putative kinase (PINK)1 are two critical proteins associated with the pathogenesis of PD. α-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate α-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with α-syn mainly in the cytoplasm, where it initiates autophagy...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933212/impact-of-traumatic-brain-injury-on-dopaminergic-transmission
#10
Yuan-Hao Chen, Eagle Yi-Kung Huang, Tung-Tai Kuo, Jonathan Miller, Yung-Hsiao Chiang, Barry J Hoffer
Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine (DA) physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after traumatic brain injury (TBI)...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28931341/the-neurotoxic-effects-of-prenatal-gabapentin-and-oxcarbazepine-exposure-on-newborn-rats
#11
Zuleyha Erisgin, Bulent Ayas, Jens R Nyengaard, N Ercument Beyhun, Yuksel Terzi
Teratogenicity is a problematic issue for pregnant women because of x-ray radiation, drugs, genetic and unknown variables. First generation antiepileptic drugs (AED) like valproic acid are well-known teratogens for developing foetuses. However, their usage is necessary in order to prevent maternal seizures. The underlying mechanism of birth defects associated with AED exposure remains unclear and information about the neurotoxic effects of prenatal exposure to AED is still limited. Oxcarbazepine (OXC) and gabapentin (GBP) are second generation antiepileptic drugs...
September 20, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28930612/genetic-addiction-risk-score-gars-%C3%A2-a-predictor-of-vulnerability-to-opioid-dependence
#12
Kenneth Blum, Amanda L C Chen, Panayotis K Thanos, Marcelo Febo, Zsolt Demetrovics, Kristina Dushaj, Abraham Kovoor, David Baron, David E Smith, Alphonso Kenison Roy Iii, Lyle Fried, Thomas J H Chen, Edwin Chapman, Edward Modestino, Bruce Steinberg, Rajendra D Badgaiyan
The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS)...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930574/food-addiction-a-common-neurobiological-mechanism-with-drug-abuse
#13
Elsa Lindgren, Kyle Gray, Gregg Miller, Ryan Tyler, Corinde E Wiers, Nora D Volkow, Gene-Jack Wang
Drugs and food both exert a rewarding effect through the firing of dopamine neurons in the ventral tegmental area, resulting in the release of dopamine into the nucleus accumbens and effects on the mesolimbic pathway. Here, we review the neuroimaging literature to consider the validity of food addiction and the common neurobiological mechanisms that overlap in food and drug addiction. This review paper focuses on findings from Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI) and structural imaging studies, as well as evidence from neuroimaging studies of bariatric surgery and pharmacological interventions on obese individuals...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930284/effects-of-intranasal-oxytocin-on-the-blood-oxygenation-level-dependent-signal-in-food-motivation-and-cognitive-control-pathways-in-overweight-and-obese-men
#14
Franziska Plessow, Dean A Marengi, Sylvia K Perry, Julia M Felicione, Rachel Franklin, Tara M Holmes, Laura M Holsen, Nikolaos Makris, Thilo Deckersbach, Elizabeth A Lawson
Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study in order to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men...
September 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28929131/spontaneous-eye-blink-rate-ebr-is-uncorrelated-with-dopamine-d2-receptor-availability-and-unmodulated-by-dopamine-agonism-in-healthy-adults
#15
Linh C Dang, Gregory R Samanez-Larkin, Jaime J Castrellon, Scott F Perkins, Ronald L Cowan, Paul A Newhouse, David H Zald
Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28928655/effects-of-simvastatin-beyond-dyslipidemia-exploring-its-antinociceptive-action-in-an-animal-model-of-complex-regional-pain-syndrome-type-i
#16
Graziela Vieira, Juliana Cavalli, Elaine C D Gonçalves, Tainara R Gonçalves, Larissa R Laurindo, Maíra Cola, Rafael C Dutra
Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP) was induced by ischemia and reperfusion (IR) injury of the left hind paw...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928373/a-synthetic-cell-permeable-antioxidant-protects-neurons-against-acute-oxidative-stress
#17
Nicola J Drummond, Nick O Davies, Janet E Lovett, Mark R Miller, Graeme Cook, Thomas Becker, Catherina G Becker, Donald B McPhail, Tilo Kunath
Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928221/upregulation-of-autophagy-related-gene-5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#18
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28927576/loss-of-microrna-7-regulation-leads-to-%C3%AE-synuclein-accumulation-and-dopaminergic-neuronal-loss-in%C3%A2-vivo
#19
Kirsty J McMillan, Tracey K Murray, Nora Bengoa-Vergniory, Oscar Cordero-Llana, Jane Cooper, Amy Buckley, Richard Wade-Martins, James B Uney, Michael J O'Neill, Liang F Wong, Maeve A Caldwell
Abnormal alpha-synuclein (α-synuclein) expression and aggregation is a key characteristic of Parkinson's disease (PD). However, the exact mechanism(s) linking α-synuclein to the other central feature of PD, dopaminergic neuron loss, remains unclear. Therefore, improved cell and in vivo models are needed to investigate the role of α-synuclein in dopaminergic neuron loss. MicroRNA-7 (miR-7) regulates α-synuclein expression by binding to the 3' UTR of the Synuclein Alpha Non A4 Component of Amyloid Precursor (SNCA) gene and inhibiting its translation...
August 31, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28924693/phosphodiesterase-4-inhibition-affects-both-the-direct-and-indirect-pathway-an-electrophysiological-study-examining-the-tri-phasic-response-in-the-substantia-nigra-pars-reticulata
#20
P R A Heckman, J V Schweimer, T Sharp, J Prickaerts, A Blokland
Fronto-striatal circuits constitute the neurobiological basis of many neuropsychiatric disorders. Part of the intracellular signaling within these circuits, including its dopaminergic modulation, is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling cascade. Based on the overall expression in human fronto-striatal circuitry, we tested the effects of a cAMP selective phosphodiesterase 4 (PDE4) inhibitor on the tri-phasic response in the dorsomedial substantia nigra pars reticulata (SNr) upon stimulation of the infralimbic cortex in rats...
September 18, 2017: Brain Structure & Function
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