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Dopamine transporter

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https://www.readbyqxmd.com/read/28445595/ventricular-fibrillation-cardiac-arrest-produces-a-chronic-striatal-hyperdopaminergic-state-that-is-worsened-by-methylphenidate-treatment
#1
Gerald J Nora, Rashed Harun, David F Fine, Daniel Hutchison, Adam C Grobart, Jason P Stezoski, Miranda Munoz, Patrick M Kochanek, Rehana K Leak, Tomas Drabek, Amy K Wagner
Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury. Currently, little is understood about chronic changes in striatal dopamine (DA) systems after hypoxic-ischemic brain injury. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA)...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#2
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28442581/sigma-receptor-effects-of-n-substituted-benztropine-analogs-implications-for-antagonism-of-cocaine-self-administration
#3
Takato Hiranita, Weimin C Hong, Theresa Kopajtic, Jonathan L Katz
Several N-substituted benztropine (BZT) analogs are atypical dopamine transport inhibitors as they have affinity for the dopamine transporter (DAT), but have minimal cocaine-like pharmacological effects and can block numerous effects of cocaine including its self-administration. Among these compounds, N-methyl (AHN1-055), N-allyl (AHN2-005), and N-butyl (JHW007) analogs of 3α-[bis(4'-fluorophenyl)methoxy]-tropane were more potent in antagonizing self-administration of cocaine and d-methamphetamine than in decreasing food-maintained responding...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28441487/the-isomeric-preference-of-an-atypical-dopamine-transporter-inhibitor-contributes-to-its-selection-of-the-transporter-conformation
#4
Ara M Abramyan, Sebastian Stolzenberg, Zheng Li, Claus J Loland, Frank Noé, Lei Shi
Cocaine, a widely abused psychostimulant, inhibits the dopamine transporter (DAT) by trapping the protein in an outward-open conformation, whereas atypical DAT inhibitors such as benztropine have low abuse liability and prefer less outward-open conformations. Here, we use a spectrum of computational modeling and simulation approaches to obtain the underlying molecular mechanism in atomistic detail. Interestingly, our quantum mechanical calculations and molecular dynamics (MD) simulations suggest that a benztropine derivative JHW007 prefers a different stereoisomeric conformation of tropane in binding to DAT compared to that of a cocaine derivative, CFT...
April 25, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28437017/determination-of-the-enantiomeric-purity-of-the-selective-dopamine-transporter-inhibitor-r-r-4-2-benzhydryloxyethyl-1-4-fluorobenzyl-piperidin-3-ol
#5
Patrick Neiens, Georg Höfner, Klaus T Wanner
(+)-R,R-D-84 ((+)-R,R-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol) is a promising pharmacological tool for the dopamine transporter (DAT), due to its high affinity and selectivity for this target. In this study, an analytical method to ascertain the enantiomeric purity of this compound was established. For this purpose, a high-performance liquid chromatographic (HPLC) method, based on a cellulose derived chiral stationary phase (CSP) was developed. The method was characterized concerning its specificity, linearity, and range...
April 24, 2017: Chirality
https://www.readbyqxmd.com/read/28433974/hypoactive-hypoalert-behaviour-and-thalamic-hypometabolism-due-to-intracranial-hypotension
#6
Seamus Kearney, Peter Flynn, Simon Hughes, Wendy Spence, Mark Owen McCarron
A 47-year-old man presented with a 9-year history of a hypoalert hypoactive behaviour syndrome, caused by the deep brain swelling variant of spontaneous intracranial hypotension. Along with apathy with retained cognition, he had stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a sagging brainstem, pointed ventricles and reduced angle between the vein of Galen and the straight sinus, but no meningeal enhancement or subdural collections. A dopamine transporter scan showed preganglionic dopamine receptor deficiency; a fluorodeoxy glucose positron emission tomography scan showed bilateral hypothalamic hypometabolism...
April 22, 2017: Practical Neurology
https://www.readbyqxmd.com/read/28431168/identifying-new-susceptibility-genes-on-dopaminergic-and-serotonergic-pathways-for-the-framing-effect-in-decision-making
#7
Xiaoxue Gao, Jinting Liu, Pingyuan Gong, Junhui Wang, Wan Fang, Hongming Yan, Lusha Zhu, Xiaolin Zhou
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing...
April 19, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/28428702/drd4-and-dat1-vntr-genotyping-in-children-with-attention-deficit-hyperactivity-disorder
#8
Ashley Stanley, K Chavda, A Subramanian, S V Prabhu, T F Ashavaid
The dopamine receptor-D4 and the dopamine transporter have been investigated for their role in attention deficit hyperactivity disorder (ADHD) in children. Reports of their genetic association with ADHD have shown mixed results. The aim of the study was to evaluate the association of variable number tandem repeats (VNTRs) of the DRD4 and DAT1 genes with ADHD in children. A pilot 1:1 case control study, with 44 clinically confirmed ADHD cases and 44 age/gender matched healthy controls, was conducted at a tertiary care centre in Mumbai...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28428472/examination-of-a-method-to-determine-the-reference-region-for-calculating-the-specific-binding-ratio-in-dopamine-transporter-imaging
#9
Ayumi Watanabe, Yusuke Inoue, Yuji Asano, Kei Kikuchi, Hiroki Miyatake, Takanobu Tokushige
The specific binding ratio (SBR) was first reported by Tossici-Bolt et al. for quantitative indicators for dopamine transporter (DAT) imaging. It is defined as the ratio of the specific binding concentration of the striatum to the non-specific binding concentration of the whole brain other than the striatum. The non-specific binding concentration is calculated based on the region of interest (ROI), which is set 20 mm inside the outer contour, defined by a threshold technique. Tossici-Bolt et al. used a 50% threshold, but sometimes we couldn't define the ROI of non-specific binding concentration (reference region) and calculate SBR appropriately with a 50% threshold...
2017: Nihon Hoshasen Gijutsu Gakkai Zasshi
https://www.readbyqxmd.com/read/28427995/conditioned-taste-avoidance-conditioned-place-preference-and-hyperthermia-induced-by-the-second-generation-bath-salt-%C3%AE-pyrrolidinopentiophenone-%C3%AE-pvp
#10
Katharine H Nelson, Briana J Hempel, Matthew M Clasen, Kenner C Rice, Anthony L Riley
BACKGROUND: α-Pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP's aversive and rewarding effects...
April 17, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28421605/cholinergic-glutamatergic-co-transmission-in-striatal-cholinergic-interneurons-new-mechanisms-regulating-striatal-computation
#11
REVIEW
Ornela Kljakic, Helena Janickova, Vania F Prado, Marco A M Prado
It is well established that neurons secrete neuropeptides and ATP with classical neurotransmitters; however, certain neuronal populations are also capable of releasing two classical neurotransmitters by a process named co-transmission. Although there has been progress in our understanding of the molecular mechanism underlying co-transmission, the individual regulation of neurotransmitter secretion and the functional significance of this neuronal 'bilingualism' is still unknown. Striatal cholinergic interneurons (CINs) have been shown to secrete glutamate (Glu) in addition to acetylcholine (ACh) and are recognized for their role in the regulation of striatal circuits and behavior...
April 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28418820/case-241-hemiparkinsonism-hemiatrophy-spect-with-99m-tc-trodat-1-and-muscle-mr-imaging-abnormalities
#12
Thiago Cardoso Vale, Flávia Cristina de Lima Pinto, José Luiz Pedroso, Marília Alves Dos Reis, Ilza Rosa Batista, Rodrigo Affonseca Bressan, René Leandro Magalhães Rivero, Renato Adam Mendonça, Orlando G Barsottini
History A 43-year-old right-handed man presented with a history of progressive mild left-sided weakness and slowness of movements. Symptoms began 4 years earlier, and the patient noticed a progressive decline in his daily routine due to gait difficulties in the past year. There was no history of head trauma, surgery, drug therapy, smoking, or alcohol abuse, nor was there any relevant family history. Examination revealed normal cognition (29 of 30 points on the Mini-Mental State Examination and 27 of 30 points on the Montreal Cognitive Assessment) and normal cerebellar, sensory, cranial nerve, and autonomic function...
May 2017: Radiology
https://www.readbyqxmd.com/read/28417953/recombinant-adeno-associated-virus-mediated-rescue-of-function-in-a-mouse-model-of-dopamine-transporter-deficiency-syndrome
#13
P Illiano, C E Bass, L Fichera, L Mus, E A Budygin, T D Sotnikova, D Leo, S Espinoza, R R Gainetdinov
Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene, leading to severe neurological disabilities in children and adults. DAT-Knockout (DAT-KO) mouse is currently the best animal model for this syndrome, displaying functional hyperdopaminergia and neurodegenerative phenotype leading to premature death in ~36% of the population. We used DAT-KO mouse as model for DTDS to explore the potential utility of a novel combinatorial adeno-associated viral (AAV) gene therapy by expressing DAT selectively in DA neurons and terminals, resulting in the rescue of aberrant striatal DA dynamics, reversal of characteristic phenotypic and behavioral abnormalities, and prevention of premature death...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414692/neuronal-fibers-and-neurotransmitter-receptor-expression-in-the-human-endolymphatic-sac
#14
Martin Nue Møller, Svend Kirkeby, Jonas Vikeså, Finn Cilius Nielsen, Per Cayé-Thomasen
INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may have multiple functions, including an ion-transport capacity comparable to the kidney, an immunological capacity and a possible natriuretic capacity. Further, there have been speculations of a yet undefined role in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES...
April 14, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28413401/parkinsonism-in-association-with-dihydropteridine-reductase-deficiency
#15
Yoshiaki Takahashi, Yasuhiro Manabe, Yumiko Nakano, Taijun Yunoki, Syoichiro Kono, Hisashi Narai, Mahoko Furujo, Koji Abe
We report a 16-year-old man with disorders of tetrahydrobiopterin metabolism due to dihydropteridine reductase (DHPR) deficiency. He revealed moderate mental retardation, parkinsonism, and spastic paralysis with levodopa and 5-hydroxytryptophan (5-HTP) supplementation from the age of 2 months. Brain MRI showed high intensity areas in bilateral frontal and posterior deep white matter on fluid-attenuated inversion recovery (FLAIR). Coronal FLAIR image showed a high signal in bilateral pyramidal tracts. Single photon computed tomography (SPECT) imaging of the dopamine transporter was normal...
January 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28412373/mechanistic-evaluation-of-tapentadol-in-reducing-the-pain-perception-using-in-vivo-brain-and-spinal-cord-microdialysis-in-rats
#16
Vijay Benade, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Saivishal Daripelli, Ganesh Ayyanki, Shantaveer Irappanavar, Ranjithkumar Ponnamaneni, Arunkumar Manoharan
Role of monoamine neurotransmitters in the modulation of emotional and pain processing in spinal cord and brain regions is not well known. Tapentadol, a norepinephrine reuptake inhibitor with µ-opioid receptor agonistic activity has recently been introduced for the treatment of moderate to severe pain. The objective of the present study was to examine the effects of tapentadol on modulation of monoamines in the prefrontal cortex and dorsal horn using brain microdialysis. Tapentadol was administered intraperitoneally at 4...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28411257/relief-of-pain-depressed-behavior-in-rats-by-activation-of-d1-like-dopamine-receptors
#17
Matthew F Lazenka, Kelen C Freitas, Sydney Henck, S Stevens Negus
Clinically significant pain often includes depression of both behavior and mesolimbic dopamine signaling. Indirect and/or direct dopamine receptor agonists may alleviate pain-related behavioral depression. To test this hypothesis, the present study compared effects of indirect and direct dopamine agonists in a preclinical assay of pain-depressed operant responding. Male Sprague-Dawley rats with chronic indwelling microelectrodes in the medial forebrain bundle were trained in an intracranial self-stimulation (ICSS) procedure to press a lever for pulses of electrical brain stimulation...
April 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28410288/the-utility-of-the-combination-of-a-spect-study-with-123i-fp-cit-of-dopamine-transporters-and-123i-mibg-myocardial-scintigraphy-in-differentiating-parkinson-disease-from-other-degenerative-parkinsonian-syndromes
#18
Naoto Uyama, Hideki Otsuka, Takayoshi Shinya, Yoichi Otomi, Masafumi Harada, Wataru Sako, Yuishin Izumi, Ryuji Kaji, Yuya Watanabe, Satoru Takashi, Yamato Kunikane
OBJECTIVE: Molecular imaging of nigrostriatal dopamine transporters (DAT) and sympathetic cardiac innervation with single-photon emission computed tomography (SPECT) are useful tools for differentiating idiopathic Parkinson disease (PD) from other degenerative parkinsonian syndromes (non-PD). Nevertheless, these modalities are often insufficient for achieving a definite diagnosis. The aims of this study were to evaluate the diagnostic accuracy of the combination of these tools. MATERIALS AND METHODS: The SPECT radiotracers [I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane (FP-CIT) and meta-[I]-iodobenzylguanidine (MIBG) were used to research presynaptic dopaminergic projections (DAT SPECT) and myocardial adrenergic innervation (MIBG scintigraphy), respectively...
April 13, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#19
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28409750/clinical-characteristics-of-parkinson-s-disease-developed-from-essential-tremor
#20
Dong-Woo Ryu, Si-Hoon Lee, Yoon-Sang Oh, Jae-Young An, Jeong-Wook Park, In-Uk Song, Kwang-Soo Lee, Joong-Seok Kim
BACKGROUND: Recent genetic and epidemiological studies have shown that there is a link between essential tremor and Parkinson's disease (PD). However, there is a lack of data about the clinical features of PD developed from essential tremor. OBJECTIVE: To explore and describe the clinical characteristics of Parkinson's disease developed from essential tremor (ET-PD). METHODS: Twenty-five ET-PD patients and 124 IPD controls were enrolled according to each criterion...
April 13, 2017: Journal of Parkinson's Disease
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