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Martin J Bobak, Matthew W Weber, Melissa A Doellman, Douglas R Schuweiler, Jeana M Athens, Steven A Juliano, Paul A Garris
Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders, but its mechanism is incompletely understood. Compared to other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling...
October 12, 2016: Journal of Pharmacology and Experimental Therapeutics
Morgane Milienne-Petiot, James P Kesby, Mary Graves, Jordy van Enkhuizen, Svetlana Semenova, Arpi Minassian, Athina Markou, Mark A Geyer, Jared W Young
BACKGROUND: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses...
October 9, 2016: Neuropharmacology
Dat T Tran, Arto Ohinmaa, Nguyen X Thanh, Jonathan G Howlett, Justin A Ezekowitz, Finlay A McAlister, Padma Kaul
BACKGROUND: Heart failure is a costly health condition and a major public health concern. We sought to examine the costs of hospital admissions for heart failure between fiscal years 2004 and 2013 in Canada and to model the future costs to 2030. METHODS: Canadian Institutes for Health Information Discharge Abstract Database was used to identify admissions to hospital with heart failure as the primary diagnosis between fiscal years 2004 and 2013. Multiple linear regression models were used to calculate the trend in prevalence and extrapolate these to 2030...
July 2016: CMAJ Open
Wang Yan, Zhao-Ying Chen, Jia-Qi Chen, Hui-Min Chen
BACKGROUND: Neural stem cells (NSCs) are pluripotent and self-renewing cells which could differentiate into diverse types of neural cells, such as dopaminergic (DA) neurons, the loss of which is the typical characteristic of Parkinson's disease (PD). This study aimed to examine the molecular mechanisms of BMP2-mediating NSCs differentiation into DA neurons. METHODS: Different concentrations of BMP2 were used to induce the differentiation of NSCs into DA neurons, which were characterized by the number and the neurite lengths of tyrosine hydroxylase (TH)+ and dopamine transporter (DAT)+ neurons by immunocytochemistry...
2016: American Journal of Translational Research
P Schwingenschuh, G Deuschl
Functional tremor is the commonest reported functional movement disorder. A confident clinical diagnosis of functional tremor is often possible based on the following "positive" criteria: a sudden tremor onset, unusual disease course, often with fluctuations or remissions, distractibility of the tremor if attention is removed from the affected body part, tremor entrainment, tremor variability, and a coactivation sign. Many patients show excessive exhaustion during examination. Other somatizations may be revealed in the medical history and patients may show additional functional neurologic symptoms and signs...
2017: Handbook of Clinical Neurology
Chi Wang Ip, Ioannis U Isaias, Burak B Kusche-Tekin, Dennis Klein, Janos Groh, Aet O'Leary, Susanne Knorr, Takahiro Higuchi, James B Koprich, Jonathan M Brotchie, Klaus V Toyka, Andreas Reif, Jens Volkmann
Isolated generalized dystonia is a central motor network disorder characterized by twisted movements or postures. The most frequent genetic cause is a GAG deletion in the Tor1a (DYT1) gene encoding torsinA with a reduced penetrance of 30-40 % suggesting additional genetic or environmental modifiers. Development of dystonia-like movements after a standardized peripheral nerve crush lesion in wild type (wt) and Tor1a+/- mice, that express 50 % torsinA only, was assessed by scoring of hindlimb movements during tail suspension, by rotarod testing and by computer-assisted gait analysis...
October 3, 2016: Acta Neuropathologica Communications
Maria Salsone, Rita Nistico', Basilio Vescio, Fabiana Novellino, Maurizio Morelli, Angela Lupo, Gennarina Arabia, Aldo Quattrone
OBJECTIVE: To investigate heart rate variability (HRV) in patients with Essential Tremor (ET) in comparison with patients with Parkinson's Disease (PD). METHODS: This is a cross sectional control study including 10 patients with ET, 10 patients with PD and 10 age-sex-matched controls. In patients and controls, we measured the components of HRV analysis in the frequency domain during a daytime period of 12-h. Selected HRV variables were low-frequency (LF) and high-frequency (HF), conventionally considered to be influenced by the sympathetic system and the parasympathetic system respectively...
September 28, 2016: Parkinsonism & related Disorders
S Stevens Negus, Matthew L Banks
Many cathinone analogs act as substrates or inhibitors at dopamine, norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine transporter substrates and inhibitors, such that potency at DAT > SERT is associated with high abuse potential, whereas potency at DAT < SERT is associated with low abuse potential. Quantitative structure-activity relationship (QSAR) studies with a series of 4-substituted methcathinone analogs identified volume of the 4-position substituent on the methcathinone phenyl ring as one structural determinant of both DAT vs...
October 1, 2016: Current Topics in Behavioral Neurosciences
Aleksandra Kornacka, Aleksandra Cybulska, Justyna Bień, Katarzyna Goździk, Bożena Moskwa
The aim of the study was to compare the usefulness of two antibody-based methods, the direct agglutination test (DAT) and enzyme linked immuosorbent assay (ELISA), with that of the polymerase chain reaction (PCR) for detecting anti-Toxoplasma gondii in samples derived from naturally-infected wild animals. Antibodies against T. gondii were detected in meat juice samples collected from 129 free- living carnivores and omnivores. T. gondii seroprevalence was confirmed in 73,6% of examined samples when DAT and ELISA were used separately, but in only 88,4% samples when both immunological tests were used in parallel...
September 15, 2016: Veterinary Parasitology
Ashlee Van't Veer, Karen L Smith, Bruce M Cohen, William A Carlezon, Anita J Bechtholt
INTRODUCTION: Studies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front-line treatment for alcoholism in humans. Although roles for mu- and delta-opioid receptors have been characterized, the contribution of kappa-opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions...
September 2016: Brain and Behavior
Alissa C Rothchild, James R Sissons, Shahin Shafiani, Christopher Plaisier, Deborah Min, Dat Mai, Mark Gilchrist, Jacques Peschon, Ryan P Larson, Andreas Bergthaler, Nitin S Baliga, Kevin B Urdahl, Alan Aderem
The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Khanh V Doan, Ann W Kinyua, Dong Joo Yang, Chang Mann Ko, Sang Hyun Moh, Ko Eun Shong, Hail Kim, Sang-Kyu Park, Dong-Hoon Kim, Inki Kim, Ji-Hye Paik, Ronald A DePinho, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Yun-Hee Choi, Ki Woo Kim
Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KO(DAT)) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis...
2016: Nature Communications
Panayotis K Thanos, Jianmin Zhuo, Lisa Robison, Ronald Kim, Mala Ananth, Ilon Choai, Adam Grunseich, Nicola M Grissom, Robert George, Foteini Delis, Teresa M Reyes
Birthweight is a marker for suboptimal fetal growth and development in utero. Offspring can be born large for gestational age (LGA), which is linked to maternal obesity or excessive gestational weight gain, as well as small for gestational age (SGA), arising from nutrient or calorie deficiency, placental dysfunction, or other maternal conditions (hypertension, infection). In humans, LGA and SGA babies are at an increased risk for certain neurodevelopmental disorders, including Attention Deficit/Hyperactivity Disorder, schizophrenia, and social and mood disorders...
September 22, 2016: International Journal of Developmental Neuroscience
Zhongjian Cheng, Venkata Garikipati, Emily Nickoloff, Chunlin Wang, David J Polhemus, Jibin Zhou, Cynthia Benedict, Mohsin Khan, Suresh K Verma, Joseph E Rabinowitz, David Lefer, Raj Kishore
BACKGROUND: -Bone marrow cell-based treatment for critical limb ischemia (CLI) in diabetic patients yielded a modest therapeutic effect due to cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypotheses that restoration of hydrogen sulfide (H2S) production in diabetic bone marrow cells (BMCs) improves their reparative capacities. METHODS: -Mouse BMCs were isolated by density-gradient centrifugation...
September 22, 2016: Circulation
Michał Kijak, Sebastian Peukert, Ephriem Mengesha, Jerzy Sepioł, Michał Gil
We report on laser-induced fluorescence excitation and dispersed fluorescence spectra of two isomeric compounds: 1,4- and 1,8-diazatriphenylene (1,4- and 1,8-DAT) isolated in supersonic molecular jets, and their 1:1 complexes with protic solvents. We found that the ground and excited state vibronic patterns of bare 1,4-DAT differ significantly from those of 1,8-DAT, and those of the complexes of both isomers. A marked activity of several out-of-plane vibrations in 1,4-DAT and the symptoms of the distortion of the S1 excited molecule were diagnosed from the vibronic spectra, whereas planar structures were predicted for 1,8-DAT in S0 and S1 states...
October 4, 2016: Journal of Physical Chemistry. A
S F Sacuiu
This chapter will focus on the descriptive, analytic, and intervention-oriented epidemiology of dementia and its most frequent etiologic type due to Alzheimer's disease. The chapter opens with a brief presentation of the concept of dementia, followed by the presentation of dementia of the Alzheimer type (DAT), including natural history, clinical manifestation, neuropathology, medical prognosis, and management. Further, the chapter presents the prevalence and incidence of dementia, with special consideration of secular trends in prevalence and incidence of DAT, and prognosis of the socioeconomic impact of dementia...
2016: Handbook of Clinical Neurology
Xiaojian Jia, Feng Wang, Ying Han, Xuewen Geng, Minghua Li, Yu Shi, Lin Lu, Yun Chen
The dopamine transporter (DAT) is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neurotransmission. In the present study, we found that miR-137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine transport. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced...
September 15, 2016: Neuroscience Bulletin
Ruth I Versteeg, Karin E Koopman, Jan Booij, Mariëtte T Ackermans, Unga A Unmehopa, Eric Fliers, Susanne E la Fleur, Mireille J Serlie
BACKGROUND: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. METHODS: We performed a case-control study in insulin sensitive obese (ISO) and insulin resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using 123I-FP-CIT single photon emission computed tomography (SPECT)...
September 14, 2016: Neuroendocrinology
Karina A Top, Marie-Noelle Billard, Marie-Claude Gariepy, Isabelle Rouleau, Jeffrey M Pernica, Anne Pham-Huy, Caroline Quach, Dat Tran, Wendy Vaudry, Simon Dobson, François D Boucher, Alex Carignan, Taj Jadavji, Athena McConnell, Shelly A McNeil, Scott A Halperin, Gaston De Serres
BACKGROUND: For patients who have experienced adverse events following immunization (AEFI) or who have specific medical conditions, there is limited evidence regarding the best approach to immunization. The Special Immunization Clinics (SIC) Network was established to standardize patient management and assess outcomes after re-immunization. The study objective was to describe the first two years of the network's implementation. METHODS: Twelve SICs were established across Canada by infectious diseases specialists and allergists...
September 12, 2016: Pediatric Infectious Disease Journal
Victoria Sanchez, Marco D Carpenter, Nicole L Yohn, Julie A Blendy
RATIONALE: Prescription opioid abuse and transition to heroin use are growing problems in the USA. However, the long-term consequences of adolescent prescription opioid abuse on subsequent drug use and affective-like behavior are unknown. OBJECTIVES: This study aims to determine if adolescent exposure to oxycodone alters the rewarding effects of morphine, anxiety-like behavior, and reward-related gene expression later in adulthood. METHODS: Adolescent male C57Bl/6 mice were exposed to oxycodone (3 mg/kg/day) via osmotic minipumps for 28 days...
September 13, 2016: Psychopharmacology
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