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https://www.readbyqxmd.com/read/28223522/conformational-dynamics-of-a-neurotransmitter-sodium-symporter-in-a-lipid-bilayer
#1
Suraj Adhikary, Daniel J Deredge, Anu Nagarajan, Lucy R Forrest, Patrick L Wintrode, Satinder K Singh
Neurotransmitter:sodium symporters (NSSs) are integral membrane proteins responsible for the sodium-dependent reuptake of small-molecule neurotransmitters from the synaptic cleft. The symporters for the biogenic amines serotonin (SERT), dopamine (DAT), and norepinephrine (NET) are targets of multiple psychoactive agents, and their dysfunction has been implicated in numerous neuropsychiatric ailments. LeuT, a thermostable eubacterial NSS homolog, has been exploited as a model protein for NSS members to canvass the conformational mechanism of transport with a combination of X-ray crystallography, cysteine accessibility, and solution spectroscopy...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28220701/deconstructed-analogs-of-bupropion-reveal-structural-requirements-for-transporter-inhibition-versus-substrate-induced-neurotransmitter-release
#2
Abdelrahman R Shalabi, Donna Walther, Michael H Baumann, Richard A Glennon
Bupropion (1), an α-aminophenone uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET), is a widely prescribed antidepressant and smoking cessation aid. Cathinone (2), a structurally simpler α-aminophenone, is a substrate-type releasing agent at the same transporters and a recognized drug of abuse. Our goal was to identify the structural features of α-aminophenones that govern the mechanistic transition from uptake inhibition to substrate-induced release. Deconstructed analogs of 1 were synthesized and compared for their ability to interact with DAT, NET, and the serotonin transporter (SERT) using in vitro assay methods...
February 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28206711/localization-patterns-of-dopamine-active-transporter-synthesizing-cells-during-development-of-brine-shrimp
#3
Bo Yong Kim, Gyeong Hee Shin, In Soo Lee, Suhng Wook Kim, Ho Seung Kim, Jin Kwan Kim, Seung Gwan Lee
There have been many studies on dopamine active transporter (DAT) in humans and laboratory animals; however, there is a lack of information on DAT in brine shrimp. In this study, we demonstrated the neuronal and nonneuronal characteristics of DAT-synthesizing (DAT(+) cells) during development of brine shrimp. In neuronal cells, the DAT(+) neurons in the central body and lobes of a protocerebrum (PC) controlled the deutocerebrum. The sensory cells of nauplius eyes projected their decussated axons to the PC, and the DAT(+) cells at the posterior region were associated with migration and control of the 10 posterior neurons during the early nauplius stage...
February 16, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28194630/source-based-morphometry-multivariate-approach-to-analyze-123-i-fp-cit-spect-imaging
#4
Enrico Premi, V D Calhoun, V Garibotto, R Turrone, A Alberici, E Cottini, A Pilotto, S Gazzina, M Magoni, B Paghera, B Borroni, A Padovani
PURPOSE: [(123)I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [(123)I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks...
February 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28192111/effects-of-progesterone-administered-after-mptp-on-dopaminergic-neurons-of-male-mice
#5
Nadhir Litim, Marc Morissette, Thérèse Di Paolo
Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28186690/reduced-levels-of-cacna1c-attenuate-mesolimbic-dopamine-system-function
#6
Chantelle E Terrillion, David T Dao, Roger Cachope, Mary Kay Lobo, Adam C Puche, Joseph F Cheer, Todd D Gould
Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Cav 1.2, is associated with clinical diagnoses of bipolar disorder, depression, and schizophrenia. Dysregulation of the mesolimbic dopamine (DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk...
February 10, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28182634/the-slc6a3-gene-possibly-affects-susceptibility-to-late-onset-alcohol-dependence-but-not-specific-personality-traits-in-a-han-chinese-population
#7
Chang-Chih Huang, Shin-Chang Kuo, Yi-Wei Yeh, Chun-Yen Chen, Che-Hung Yen, Chih-Sung Liang, Pei-Shen Ho, Ru-Band Lu, San-Yuan Huang
Dopaminergic dysfunction has an important role in the pathoetiology of alcohol dependence (AD). The purpose of this study was to determine whether the solute carrier family 6 member 3 (SLC6A3) gene (also known as the dopamine transporter DAT gene) was associated with AD, and whether variants in the SLC6A3 locus were associated with specific personality traits in patients with AD. Sixteen polymorphisms in SLC6A3 were analyzed using 637 patients with AD and 523 healthy controls. To reduce clinical heterogeneity, patients were classified into two subgroups: early-onset AD (EOAD) and late-onset AD (LOAD)...
2017: PloS One
https://www.readbyqxmd.com/read/28167616/towards-trans-diagnostic-mechanisms-in-psychiatry-neurobehavioral-profile-of-rats-with-a-loss-of-function-point-mutation-in-the-dopamine-transporter-gene
#8
Valentina Vengeliene, Anton Bespalov, Martin Roßmanith, Sandra Horschitz, Stefan Berger, Ana L Relo, Hamid R Noori, Peggy Schneider, Thomas Enkel, Dusan Bartsch, Miriam Schneider, Berthold Behl, Anita C Hansson, Patrick Schloss, Rainer Spanagel
The Research Domain Criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here we used a new genetic rat model with a loss of function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix (www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml). First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains - negative and positive valence systems, cognitive, social, and in arousal/regulatory systems...
February 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28163218/atypical-dopamine-efflux-caused-by-3-4-methylenedioxypyrovalerone-mdpv-via-the-human-dopamine-transporter
#9
Aparna Shekar, Jenny I Aguilar, Greta Galli, Nicholas V Cozzi, Simon D Brandt, Arnold E Ruoho, Michael H Baumann, Heinrich J G Matthies, Aurelio Galli
Synthetic cathinones are similar in chemical structure to amphetamines, and their behavioral effects are associated with enhanced dopaminergic signaling. The past ten years of research on the common constituent of bath salts, MDPV (the synthetic cathinone 3,4-methylenedioxypyrovalerone), has aided the understanding of how synthetic cathinones act at the dopamine (DA) transporter (DAT). Several groups have described the ability of MDPV to block the DAT with high-affinity. In this study, we demonstrate for the first time a new mode of action of MDPV, namely its ability to promote DAT-mediated DA efflux...
February 3, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28160035/brexpiprazole-reduces-hyperactivity-impulsivity-and-risk-preference-behavior-in-mice-with-dopamine-transporter-knockdown-a-model-of-mania
#10
Morgane Milienne-Petiot, Mark A Geyer, Jørn Arnt, Jared W Young
RATIONALE: Bipolar disorder (BD) is a unique mood disorder defined by periods of depression and mania. The defining diagnosis of BD is the presence of mania/hypomania, with symptoms including hyperactivity and risk-taking. Since current treatments do not ameliorate cognitive deficits such as risky decision-making, and impulsivity that can negatively affect a patient's quality of life, better treatments are needed. OBJECTIVES: Here, we tested whether acute treatment with brexpiprazole, a serotonin-dopamine activity modulator with partial agonist activity at D2/3 and 5-HT1A receptors, would attenuate the BD mania-relevant behaviors of the dopamine transporter (DAT) knockdown mouse model of mania...
February 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28155214/ra-differentiation-enhances-dopaminergic-features-changes-redox-parameters-and-increases-dopamine-transporter-dependency-in-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-cells
#11
Fernanda M Lopes, Leonardo Lisbôa da Motta, Marco A De Bastiani, Bianca Pfaffenseller, Bianca W Aguiar, Luiz F de Souza, Geancarlo Zanatta, Daiani M Vargas, Patrícia Schönhofen, Giovana F Londero, Liana M de Medeiros, Valder N Freire, Alcir L Dafre, Mauro A A Castro, Richard B Parsons, Fabio Klamt
Research on Parkinson's disease (PD) and drug development is hampered by the lack of suitable human in vitro models that simply and accurately recreate the disease conditions. To counteract this, many attempts to differentiate cell lines, such as the human SH-SY5Y neuroblastoma, into dopaminergic neurons have been undertaken since they are easier to cultivate when compared with other cellular models. Here, we characterized neuronal features discriminating undifferentiated and retinoic acid (RA)-differentiated SH-SYSY cells and described significant differences between these cell models in 6-hydroxydopamine (6-OHDA) cytotoxicity...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28154545/influence-of-the-slc6a3-dat1-gene-on-multifaceted-measures-of-self-regulation-in-preschool-children
#12
Lina M Cómbita, Pascale Voelker, Alicia Abundis-Gutiérrez, Joan P Pozuelos, M Rosario Rueda
Development of self-regulation, the capacity to voluntarily modulate thoughts, emotions and actions is strongly related to the maturation of the dopamine-mediated executive attention network (EAN). The attention control processes associated with the EAN greatly overlap with efficiency of the executive functions and are correlated with measures of effortful control. Regulation of dopamine levels within the EAN, particularly in the basal ganglia is carried out by the action of dopamine transporters. In humans, the SLC6A3/DAT1 gene carries out the synthesis of the DAT protein...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28143577/aav1-2-induced-overexpression-of-a53t-%C3%AE-synuclein-in-the-substantia-nigra-results-in-degeneration-of-the-nigrostriatal-system-with-lewy-like-pathology-and-motor-impairment-a-new-mouse-model-for-parkinson-s-disease
#13
Chi Wang Ip, Laura-Christin Klaus, Akua A Karikari, Naomi P Visanji, Jonathan M Brotchie, Anthony E Lang, Jens Volkmann, James B Koprich
α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson's disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5...
February 1, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28131193/the-heterozygous-r1441c-mutation-of-leucine-rich-repeat-kinase-2-gene-in-a-chinese-patient-with-parkinson-disease-a-five-year-follow-up-and-literatures-review
#14
Fang Peng, Yi-Min Sun, Chen Chen, Su-Shan Luo, Da-Ke Li, Yi-Xuan Wang, Ke Yang, Feng-Tao Liu, Chuan-Tao Zuo, Zheng-Tong Ding, Yu An, Jian-Jun Wu, Jian Wang
BACKGROUND: Leucine-rich repeat kinase 2 gene (LRRK2) was recognized associated with both familial and sporadic Parkinson Disease (PD). Seven missense mutations (G2019S, R1441C, R1441G, R1441H, Y1699C, I2020T, N1437H) of it have been confirmed disease- causing. They were common among Caucasian PD patients, but rarely reported in Asian, especially in Chinese Han population. OBJECTIVES: We aimed to identify the frequencies of these seven mutations of LRRK2 in Chinese early-onset PD (EOPD) patients and analyze the phenotypes...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28131191/potential-multisystem-degeneration-in-asidan-patients
#15
Yasuyuki Ohta, Toru Yamashita, Nozomi Hishikawa, Kota Sato, Kosuke Matsuzono, Keiichiro Tsunoda, Noriko Hatanaka, Mami Takemoto, Toshihiko Takemi, Kazuhiro Takamatsu, Koji Abe
OBJECTIVE: To evaluate a potential multisystem involvement of neurodegeneration in Asidan, in addition to cerebellar ataxia and signs of motor neuron disease. METHODS: We compared the new Asidan patients and those identified in previous studies with Parkinson's disease (PD, n=21), and progressive supranuclear palsy (PSP, n=13) patients using (123)I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy (Asidan, DAT: n=10; MIBG: n=15)...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28130808/the-usefulness-of-combined-brain-perfusion-single-photon-emission-computed-tomography-dopamine-transporter-single-photon-emission-computed-tomography-and-123-i-metaiodobenzylguanidine-myocardial-scintigraphy-for-the-diagnosis-of-dementia-with-lewy-bodies
#16
Seiju Kobayashi, Kanae Makino, Shigeki Hatakeyama, Takao Ishii, Masaru Tateno, Tomo Iwamoto, Hanako Tsujino, Kazuhito Kawasaki, Kouhei Mikuni, Wataru Ukai, Tomonori Murayama, Eri Hashimoto, Kumiko Utsumi, Chiaki Kawanishi
BACKGROUND: Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), (123) I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT...
January 28, 2017: Psychogeriatrics: the Official Journal of the Japanese Psychogeriatric Society
https://www.readbyqxmd.com/read/28130765/-123-i-fp-cit-enc-dat-normal-database-the-impact-of-the-reconstruction-and-quantification-methods
#17
Livia Tossici-Bolt, John C Dickson, Terez Sera, Jan Booij, Susanne Asenbaun-Nan, Maria C Bagnara, Thierry Vander Borght, Cathrine Jonsson, Robin de Nijs, Swen Hesse, Pierre M Koulibaly, Umit O Akdemir, Michel Koole, Klaus Tatsch, Andrea Varrone
BACKGROUND: [(123)I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [(123)I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections...
December 2017: EJNMMI Physics
https://www.readbyqxmd.com/read/28125506/oral-modafinil-facilitates-intracranial-self-stimulation-in-rats-comparison-with-methylphenidate
#18
Matthew F Lazenka, S Stevens Negus
Modafinil is a low-potency inhibitor of dopamine transporters (DAT) approved clinically to promote wakefulness. In most procedures used for abuse-liability assessment, modafinil produces effects similar to those of abused DAT inhibitors such as cocaine and methylphenidate, although modafinil often shows lower effectiveness. However, modafinil has failed to maintain drug self-administration or produce conditioned place preferences in rats. The low potency and poor solubility of modafinil complicate its delivery by parenteral routes of administration commonly used in rats, and this may contribute toward negative results...
January 25, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28118712/effect-of-dimerization-on-the-dynamics-of-neurotransmitter-sodium-symporters
#19
Mert Gur, Mary Hongying Cheng, Elia Zomot, Ivet Bahar
Dimerization is a common feature among the members of the neurotransmitter:sodium symporter (NSS) family of membrane proteins. Yet, the effect of dimerization on the mechanism of action of NSS members is not fully understood. In this study, we examined the collective dynamics of two members of the family, leucine transporter (LeuT) and dopamine transporter (DAT), to assess the significance of dimerization in modulating the functional motions of the monomers. We used to this aim the Anisotropic Network Model (ANM), an efficient and robust method for modeling the intrinsic motions of proteins and their complexes...
January 25, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28116523/chronic-oral-methylphenidate-treatment-reversibly-increases-striatal-dopamine-transporter-and-dopamine-type-1-receptor-binding-in-rats
#20
Lisa S Robison, Mala Ananth, Michael Hadjiargyrou, David E Komatsu, Panayotis K Thanos
Previously, we created an 8-h limited-access dual bottle drinking paradigm to deliver methylphenidate (MP) to rats at two dosages that result in a pharmacokinetic profile similar to patients treated for attention deficit hyperactivity disorder. Chronic treatment resulted in altered behavior, with some effects persisting beyond treatment. In the current study, adolescent male Sprague-Dawley rats were split into three groups at four weeks of age: control (water), low-dose MP (LD), and high-dose MP (HD). Briefly, 4 mg/kg (low dose; LD) or 30 mg/kg (high dose; HD) MP was consumed during the first hour, and 10 mg/kg (LD) or 60 mg/kg (HD) MP during hours two through eight...
January 23, 2017: Journal of Neural Transmission
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