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https://www.readbyqxmd.com/read/27917309/deutetrabenazine-in-tics-associated-with-tourette-syndrome
#1
Joseph Jankovic, Joohi Jimenez-Shahed, Cathy Budman, Barbara Coffey, Tanya Murphy, David Shprecher, David Stamler
BACKGROUND: Deutetrabenazine, an inhibitor of vesicular monoamine transporter type 2 (VMAT2) depletes presynaptic dopamine and is useful in the treatment of hyperkinetic movement disorders. This study explored the safety, tolerability, and preliminary efficacy of deutetrabenazine in adolescents with moderate-to-severe tics associated with Tourette syndrome (TS). METHODS: In this open-label study of 12-18-year-old patients with TS-related tics, deutetrabenazine was titrated up to 36 mg/day over 6 weeks to adequately suppress tics without bothersome adverse effects (AEs), followed by maintenance at optimal dose for 2 weeks...
2016: Tremor and Other Hyperkinetic Movements
https://www.readbyqxmd.com/read/27917116/preliminary-evidence-of-apathetic-like-behavior-in-aged-vesicular-monoamine-transporter-2-deficient-mice
#2
Aron Baumann, Carlos G Moreira, Marta M Morawska, Sophie Masneuf, Christian R Baumann, Daniela Noain
Apathy is considered to be a core feature of Parkinson's disease (PD) and has been associated with a variety of states and symptoms of the disease, such as increased severity of motor symptoms, impaired cognition, executive dysfunction and dementia. Apart from the high prevalence of apathy in PD, which is estimated to be about 40%, the underlying pathophysiology remains poorly understood and current treatment approaches are unspecific and proved to be only partially effective. In animal models, apathy has been sub-optimally modeled, mostly by means of pharmacological and stress-induced methods, whereby concomitant depressive-like symptoms could not be ruled out...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27913432/von-economo-neurons-and-fork-cells-a-neurochemical-signature-linked-to-monoaminergic-function
#3
Anke A Dijkstra, Li-Chun Lin, Alissa L Nana, Stephanie E Gaus, William W Seeley
The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons...
December 1, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27836486/immunochemical-localization-of-vesicular-monoamine-transporter-2-vmat2-in-mouse-brain
#4
Rachel A Cliburn, Amy R Dunn, Kristen A Stout, Carlie A Hoffman, Kelly M Lohr, Alison I Bernstein, Emily J Winokur, James Burkett, Yvonne Shmitz, William M Caudle, Gary W Miller
Vesicular monoamine transporter 2 (VMAT2, SLC18A2) is a transmembrane transporter protein that packages dopamine, serotonin, norepinephrine, and histamine into vesicles in preparation for neurotransmitter release from the presynaptic neuron. VMAT2 function and related vesicle dynamics have been linked to susceptibility to oxidative stress, exogenous toxicants, and Parkinson's disease. To address a recent depletion of commonly used antibodies to VMAT2, we generated and characterized a novel rabbit polyclonal antibody generated against a 19 amino acid epitope corresponding to an antigenic sequence within the C-terminal tail of mouse VMAT2...
November 8, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27821772/emulating-proton-induced-conformational-changes-in-the-vesicular-monoamine-transporter-vmat2-by-mutagenesis
#5
Dana Yaffe, Ariela Vergara-Jaque, Lucy R Forrest, Shimon Schuldiner
Neurotransporters located in synaptic vesicles are essential for communication between nerve cells in a process mediated by neurotransmitters. Vesicular monoamine transporter (VMAT), a member of the largest superfamily of transporters, mediates transport of monoamines to synaptic vesicles and storage organelles in a process that involves exchange of two H(+) per substrate. VMAT transport is inhibited by the competitive inhibitor reserpine, a second-line agent to treat hypertension, and by the noncompetitive inhibitor tetrabenazine, presently in use for symptomatic treatment of hyperkinetic disorders...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27819145/dopamine-depleters-in-the-treatment-of-hyperkinetic-movement-disorders
#6
Joseph Jankovic
Abnormal involuntary movements often improve in response to anti-dopaminergic drugs. In contrast to classic neuroleptics that block dopamine receptors, drugs that deplete presynaptic dopamine by blocking vesicular monoamine transporter type 2 (VMAT2) seem to be safer and have little or no risk of tardive dyskinesia. This is one reason why there has been a recent emergence of novel VMAT2 inhibitors. Areas Covered: Since the approval of tetrabenazine, the classic VMAT2 inhibitor, in the treatment of chorea associated with Huntington disease (HD), other VMAT2 inhibitors (e...
November 6, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27771535/protective-effects-of-a-herbal-extract-combination-of-bupleurum-falcatum-paeonia-suffruticosa-and-angelica-dahurica-against-mptp-induced-neurotoxicity-via-regulation-of-nuclear-receptor-related-1-protein
#7
Yeomoon Sim, Gunhyuk Park, Hyeyoon Eo, Eugene Huh, Pil Sung Gu, Seon-Pyo Hong, Youngmi Kim Pak, Myung Sook Oh
Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)...
October 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27764160/csf-biomarkers-and-its-associations-with-18f-av133-cerebral-vmat2-binding-in-parkinson-s-disease-a-preliminary-report
#8
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
https://www.readbyqxmd.com/read/27736960/fuzzy-decision-making-approach-to-identify-optimum-enzyme-targets-and-drug-dosage-for-remedying-presynaptic-dopamine-deficiency
#9
Kai-Cheng Hsu, Feng-Sheng Wang
Model-based optimization approaches are valuable in developing new drugs for human metabolic disorders. The core objective in most optimal drug designs is positive therapeutic effects. In this study, we considered the effects of therapeutic, adverse, and target variation simultaneously. A fuzzy optimization method was applied to formulate a multiobjective drug design problem for detecting enzyme targets in the presynaptic dopamine metabolic network to remedy two types of enzymopathies caused by deficiencies of vesicular monoamine transporter 2 (VMAT2) and tyrosine hydroxylase (TH)...
2016: PloS One
https://www.readbyqxmd.com/read/27693414/increased-striatal-vmat2-binding-in-mice-after-chronic-administration-of-methcathinone-and-manganese
#10
Andres Asser, Sulev Kõks, Anniina Snellman, Merja Haaparanta-Solin, Eveliina Arponen, Tove Grönroos, Jaak Nairismägi, Jonas Bergquist, Ursel Soomets, Piret Piip, Mall Eltermaa, Martin Sauk, Hanna Lindmäe, Juha O Rinne, Pille Taba
Intravenous use of a psychostimulant drug containing methcathinone (ephedrone) and manganese causes an irreversible extrapyramidal syndrome in drug abusers. We aimed to reproduce the syndrome in mice to evaluate dopaminergic damage. C57/B6 mice were intraperitoneally injected once a day with the study drug or saline for a period of 27 weeks. Motor activity was recorded in an automated motility-box. After 13 and 27 weeks of treatment, ex vivo digital autoradiography was performed using [11C]dihydrotetrabenazine ([11C]DTBZ)...
September 27, 2016: Brain Research
https://www.readbyqxmd.com/read/27673755/evaluation-of-pancreatic-vmat2-binding-with-active-and-inactive-enantiomers-of-18-f-fp-dtbz-in-baboons
#11
Mika Naganawa, Shu-Fei Lin, Keunpoong Lim, David Labaree, Jim Ropchan, Paul Harris, Yiyun Huang, Masanori Ichise, Richard E Carson, Gary W Cline
INTRODUCTION: (18)F-Fluoropropyl-(+)-dihydrotetrabenazine ((18)F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about (18)F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of (18)F-FP-(+)-DTBZ and its inactive enantiomer (18)F-FP-(-)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27612194/a-novel-potential-positron-emission-tomography-imaging-agent-for-vesicular-monoamine-transporter-type-2
#12
Zih-Rou Huang, Chia-Ling Tsai, Ya-Yao Huang, Chyng-Yann Shiue, Kai-Yuan Tzen, Ruoh-Fang Yen, Ling-Wei Hsin
In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35...
2016: PloS One
https://www.readbyqxmd.com/read/27589008/vesicular-monoamine-transporters-expression-in-pheochromocytomas-and-paragangliomas-according-to-scintigraphy-and-positron-emission-tomography-behavior
#13
Alessandra Bacca, Angela Pucci, Daniele Lorenzini, Serena Chiacchio, Duccio Volterrani, Mauro Ferrari, Stefano Sellari Franceschini, Gabriele Materazzi, Fulvio Basolo, Giampaolo Bernini
BACKGROUND: The expression of vesicular catecholamine transporters (VMAT1 and 2) in pheochromocytomas (PHEOs) and paragangliomas (PGLs) and the possible relationships with [18F]FDOPA PET/CT and [123I]MIBG scintigraphy uptake are unknown. Our purpose was to investigate possible correlations of either VMAT1 and VMAT2 expression with the functional imaging in patients with PHEOs and PGLs. METHODS: An observational 3-year time study was performed by enrolling 31 consecutive patients with PHEO (n=17) or PGL (n= 14)...
September 2, 2016: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27570189/selective-accumulation-of-biotin-in-arterial-chemoreceptors-requirement-for-carotid-body-exocytotic-dopamine-secretion
#14
Patricia Ortega-Sáenz, David Macías, Konstantin L Levitsky, José A Rodríguez-Gómez, Patricia González-Rodríguez, Victoria Bonilla-Henao, Ignacio Arias-Mayenco, José López-Barneo
KEY POINTS: Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis...
August 28, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27524311/synthesis-and-in-vitro-evaluation-of-water-soluble-1-4-diphenethylpiperazine-analogs-as-novel-inhibitors-of-the-vesicular-monoamine-transporter-2
#15
Justin R Nickell, John P Culver, Venumadhav Janganati, Guangrong Zheng, Linda P Dwoskin, Peter A Crooks
A small library of 1,4-diphenethylpiperazine analogs was synthesized and evaluated for inhibition of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular monoamine transporter-2 (VMAT2). Results from these studies identified three novel molecules, 6b, 6e and 9a (Ki=35nM, 48nM and 37nM, respectively) that exhibit similar potency for inhibition of VMAT2 function compared with lobelane (Ki=45nM), and importantly, have enhanced water-solubility when compared to the previously reported 1,4-diphenethylpiperidine analogs...
September 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27520881/membrane-transporters-as-mediators-of-synaptic-dopamine-dynamics-implications-for-disease
#16
Kelly M Lohr, Shababa T Masoud, Ali Salahpour, Gary W Miller
Dopamine was first identified as a neurotransmitter localized to the midbrain over 50 years ago. The dopamine transporter (DAT; SLC6A3) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2) are two regulators of dopamine homeostasis in the presynaptic neuron. DAT transports dopamine from the extracellular space into the cytosol of the presynaptic terminal. VMAT2 then packages this cytosolic dopamine into vesicular compartments for subsequent release upon neurotransmission. Thus, DAT and VMAT2 act in concert to move transmitter efficiently throughout the neuron...
August 13, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27512998/re-cloning-the-n27-dopamine-cell-line-to-improve-a-cell-culture-model-of-parkinson-s-disease
#17
Lu Gao, Wenbo Zhou, Breanna Symmes, Curt R Freed
Parkinson's disease is characterized by the death of dopaminergic neurons in the substantia nigra. To understand the molecular mechanisms of the disease, an in vitro model is important. In the 1990s, we used the SV40 large T antigen to immortalize dopaminergic neurons derived from Embryonic Day 14 rat mesencephalon. We selected a clone for its high expression of dopaminergic neuron markers such as tyrosine hydroxylase (TH), and we named it 1RB3AN27 (N27). Because the original N27 cell line has been passaged many times, the line has become a mixture of cell types with highly variable expression of TH...
2016: PloS One
https://www.readbyqxmd.com/read/27499503/melatonin-mediated-antidepressant-like-effect-in-the-hippocampus-of-chronic-stress-induced-depression-rats-regulating-vesicular-monoamine-transporter-2-and-monoamine-oxidase-a-levels
#18
Bojana Stefanovic, Natasa Spasojevic, Predrag Jovanovic, Nebojsa Jasnic, Jelena Djordjevic, Sladjana Dronjak
The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27492886/traumatic-stress-causes-distinctive-effects-on-fear-circuit-catecholamines-and-the-fear-extinction-profile-in-a-rodent-model-of-posttraumatic-stress-disorder
#19
Chen-Cheng Lin, Che-Se Tung, Pin-Hsuan Lin, Chuen-Lin Huang, Yia-Ping Liu
Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27450565/vitamin-d-signaling-and-the-differentiation-of-developing-dopamine-systems
#20
Renata A N Pertile, Xiaoying Cui, Darryl W Eyles
Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover...
October 1, 2016: Neuroscience
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