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Dopamine transporter

Nanami Okano, Mamoru Niitsu, Junji Tanaka, Takahiro Sasaki, Kazushi Takahashi, Nobuo Araki, Toshimasa Yamamoto, Shintaro Nakano, Shigeyuki Nishimura, Takaaki Senbonmatsu, Ichiro Matsunari
PURPOSE: The aim of our study was to evaluate the use of dopamine transporter (DAT) SPECT and I-MIBG myocardial scintigraphy to determine the clinical severity of Parkinson disease (PD), with a focus on motor impairments affecting activities of daily living (ADLs). METHODS: Data for 65 consecutive PD patients who underwent both DAT and MIBG imaging were reviewed. Associations between imaging variables and Hoehn and Yahr (H&Y) staging or self-supportive care ratings were investigated...
October 21, 2016: Clinical Nuclear Medicine
Aviad Hai, Lili X Cai, Taekwan Lee, Victor S Lelyveld, Alan Jasanoff
Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe...
October 19, 2016: Neuron
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 (ST). 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
Y Kimura, J Maeda, M Yamada, K Takahata, K Yokokawa, Y Ikoma, C Seki, H Ito, M Higuchi, T Suhara
RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol...
October 20, 2016: Psychopharmacology
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
Eric Murillo-Rodríguez, Sergio Machado, Nuno Barbosa Rocha, Henning Budde, Ti-Fei Yuan, Oscar Arias-Carrión
The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents...
October 13, 2016: Neuroscience
Hong Li, Yi Jia, Xiyun Feng, Junbai Li
Inspired by the composition of adhesive proteins in mussel, a facile, low-cost, and green approach to construct robust polydopamine (PDA) microcapsules as carriers for insulin delivery is developed. The morphology and shell thickness of the capsules could be tuned by varying the concentration of dopamine or the pH of Tris-HCl buffer. The PDA capsules are stable enough for long-term storage and transportation in practical application. The fluorescent property of PDA capsules labeled with FITC is beneficial in monitoring the safety and efficacy of drug carriers...
October 5, 2016: Journal of Colloid and Interface Science
Robert S Miletich
PURPOSE OF REVIEW: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are now available for routine clinical applications in neurology. This article discusses their diagnostic use in dementia, brain tumors, epilepsy, parkinsonism, cerebrovascular disease, and traumatic brain injury. RECENT FINDINGS: Neuromolecular imaging, also known as nuclear neurology, involves clinical imaging of both basal regional physiology (perfusion, metabolism, and transport mechanisms) and specific neurochemical physiology (currently, only the dopamine transporter)...
October 2016: Continuum: Lifelong Learning in Neurology
Yaxia Yuan, Xiaoqin Huang, Jun Zhu, Chang-Guo Zhan
This is a brief review of computational modeling studies on the detailed structures and mechanism of human dopamine transporter (hDAT), as well as its interaction with HIV-1 transactivator of transcription (Tat). Extensive molecular modeling, docking and dynamics simulations have resulted in reasonable structural models of hDAT in three typical conformational states, its dopamine uptake mechanism and its interaction with Tat. The obtained hDAT models in different conformational states and their complexes with dopamine and Tat have provided novel structural and mechanistic insights concerning how hDAT uptakes dopamine and how Tat affects the dopamine uptake by hDAT...
October 14, 2016: Future Medicinal Chemistry
Chrislean Jun Botanas, Seong Shoon Yoon, June Bryan de la Peña, Irene Joy Dela Peña, Mikyung Kim, Taeseon Woo, Joung-Wook Seo, Choon-Gon Jang, Kyung-Tae Park, Young Hun Lee, Yong Sup Lee, Hee Jin Kim, Jae Hoon Cheong
The recreational use of synthetic cathinones has grown rapidly which prompted concerns from legal authorities and health care providers. However, in response to legislative regulations, synthesis of novel synthetic cathinones by introducing substituents in cathinone molecule has dramatically increased the diversity of these substances. Based on current trends, the aromatic ring is one of the popular sites in cathinone molecule being explored by designer-type modifications. In this study, we designed and synthesized a novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), which has a naphthalene substituent on the aromatic ring...
October 11, 2016: Behavioural Brain Research
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
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
Marc Pretze, Prama Pallavi, Mareike Roscher, Sarah Klotz, Julio Caballero, Uta Binzen, Wolfgang Greffrath, Rolf-Detlef Treede, Martin C Harmsen, Mathias Hafner, Benito Yard, Carmen Wängler, Björn Wängler
To mitigate pre-transplantation injury in organs of potential donors N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in brain dead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [(18)F]F-NOD [(18)F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [(18)F]5 was synthesized with reproducible high radiochemical yield and purity (>98%) as well as high specific activities (>20 GBq/µmol)...
October 12, 2016: Journal of Medicinal Chemistry
Susan W Wesmiller, Susan M Sereika, Catherine M Bender, Dana Bovbjerg, Gretchen Ahrendt, Marguerite Bonaventura, Yvette P Conley
BACKGROUND: Postoperative nausea and vomiting (PONV) are two of the most frequent and distressing complications following surgical procedures, with as many as 80% of patients considered to be at risk. Despite recognition of well-established risk factors and the subsequent use of clinical guidelines, 20-30% of women do not respond to antiemetic protocols, indicating that there may be a genetic risk. OBJECTIVE: The purpose of this pilot study was to describe the incidence and explore the risk factors associated with PONV after surgery in women diagnosed with early stage breast cancer...
September 28, 2016: Autonomic Neuroscience: Basic & Clinical
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
Sangwon Han, Minyoung Oh, Jungsu S Oh, Sang Ju Lee, Seung Jun Oh, Sun Ju Chung, Hee Kyung Park, Jae Seung Kim
Importance: Pure akinesia with gait freezing (PAGF) is a clinical syndrome characterized by freezing of gait, handwriting, and speech without abnormal eye movement or cognitive impairment. Several studies have suggested that PAGF may be a variant of progressive supranuclear palsy (PSP). However, the characteristics of striatal dopamine transporter loss in PAGF are unknown. Objective: To investigate the subregional pattern of striatal dopamine transporter loss in patients with PAGF in comparison with patients with PSP and those with Parkinson disease (PD)...
October 10, 2016: JAMA Neurology
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
Min Lin, Danielle Sambo, Habibeh Khoshbouei
: Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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