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DAT transporter

Ross McFarland, Zi Teng Wang, Yan Jouroukhin, Ye Li, Olga Mychko, Isabelle Coppens, Jianchun Xiao, Lorraine Jones-Brando, Robert H Yolken, L David Sibley, Mikhail V Pletnikov
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), has been associated with the increased risk for several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood. The T. gondii genome contains two aromatic amino acid hydroxylase genes (AAH1 and AAH2) that encode proteins that can produce L-DOPA. One popular hypothesis posits that these encoded enzymes might influence dopamine (DA) production and hence DA synaptic transmission, leading to neurobehavioral abnormalities in the infected host...
March 16, 2018: Behavioural Brain Research
Phillip Mackie, Joe Lebowitz, Leila Saadatpour, Emily Nickoloff, Peter Gaskill, Habibeh Khoshbouei
The second-most common neurodegenerative disease, Parkinson Disease (PD) has three hallmarks: dysfunctional dopamine transmission due, at least in part, to dopamine neuron degeneration; intracellular inclusions of α-synuclein aggregates; and neuroinflammation. The origin and interplay of these features remains a puzzle, as does the underlying mechanism of PD pathogenesis and progression. When viewed in the context of neuroimmunology, dopamine also plays a role in regulating peripheral immune cells. Intriguingly, plasma dopamine levels are altered in PD, suggesting collateral dysregulation of peripheral dopamine transmission...
March 15, 2018: Brain, Behavior, and Immunity
Sunao Mizumura, Kazuhiro Nishikawa, Akihiro Murata, Kosei Yoshimura, Nobutomo Ishii, Tadashi Kokubo, Miyako Morooka, Akiko Kajiyama, Atsuro Terahara
OBJECTIVE: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs...
March 15, 2018: Annals of Nuclear Medicine
Asghar M Razavi, George Khelashvili, Harel Weinstein
BACKGROUND: Much of the structure-based mechanistic understandings of the function of SLC6A neurotransmitter transporters emerged from the study of their bacterial LeuT-fold homologs. It has become evident, however, that structural differences such as the long N- and C-termini of the eukaryotic neurotransmitter transporters are involved in an expanded set of functional properties to the eukaryotic transporters. These functional properties are not shared by the bacterial homologs, which lack the structural elements that appeared later in evolution...
March 14, 2018: BMC Biology
Hiroshige Fujishiro, Masato Okuda, Kunihiro Iwamoto, Seiko Miyata, Youta Torii, Shuji Iritani, Norio Ozaki
AIMS: REM sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease / dementia with Lewy bodies. The purpose of this study is to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late-onset psychiatric disorders. METHODS: Study subjects included 19 patients with late-onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward...
March 14, 2018: Psychiatry and Clinical Neurosciences
Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Takahiro Maeki, Ryo Sasaki, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Chang Kweng Lim, Shigeru Tajima, Koji Abe
Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE...
March 9, 2018: Internal Medicine
Seok Jong Chung, Han Soo Yoo, Jungsu S Oh, Jae Seung Kim, Byoung Seok Ye, Young H Sohn, Phil Hyu Lee
INTRODUCTION: To investigate the relationship between the sub-regional pattern of striatal dopamine depletion and cognitive impairment in early-stage Parkinson's disease (PD), and determine the effect of striatal dopamine density on cognitive prognosis. METHODS: Patients with drug-naïve non-demented PD were divided into mild cognitive impairment (PD-MCI; n = 129) and cognitively normal (PD-CogN; n = 182) groups. Using quantification of the dopamine transporter (DAT) availability in each striatal sub-region with18 F-FP-CIT PET scans, we performed inter-group comparative analysis of DAT availability and multivariate linear regression analysis to assess the association between DAT availability and cognitive performance...
March 2, 2018: Parkinsonism & related Disorders
Ryul Kim, Joongyub Lee, Yoon Kim, Aryun Kim, Mihee Jang, Han-Joon Kim, Beomseok Jeon, Un Jung Kang, Stanley Fahn
INTRODUCTION: The current study was designed to determine whether the degree of presynaptic striatal dopamine depletion can predict the later development of freezing of gait (FOG) in Parkinson's disease (PD). METHODS: This retrospective cohort study included 390 de novo patients with PD without FOG at baseline. The participants were divided into tertiles according to the baseline dopamine transporter (DAT) uptake of each striatal subregion, and the cumulative risk of FOG was compared using the Kaplan-Meier method...
February 28, 2018: Parkinsonism & related Disorders
Stefano Cinque, Francesca Zoratto, Anna Poleggi, Damiana Leo, Luca Cerniglia, Silvia Cimino, Renata Tambelli, Enrico Alleva, Raul R Gainetdinov, Giovanni Laviola, Walter Adriani
Alterations in dopamine neurotransmission are generally associated with diseases such as attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Such diseases typically feature poor decision making and lack of control on executive functions and have been studied through the years using many animal models. Dopamine transporter (DAT) knockout (KO) and heterozygous (HET) mice, in particular, have been widely used to study ADHD. Recently, a strain of DAT KO rats has been developed (1)...
2018: Frontiers in Psychiatry
Jared W Young, Zackary A Cope, Benedetto Romoli, Esther Schrurs, Aniek Joosen, Jordy van Enkhuizen, Richard F Sharp, Davide Dulcis
Developing novel therapeutics for bipolar disorder (BD) has been hampered by limited mechanistic knowledge how sufferers switch between mania and depression-how the same brain can switch between extreme states-described as the "holy grail" of BD research. Strong evidence implicates seasonally-induced switching between states, with mania associated with summer-onset, depression with winter-onset. Determining mechanisms of and sensitivity to such switching is required. C57BL/6J and dopamine transporter hypomorphic (DAT-HY 50% expression) mice performed a battery of psychiatry-relevant behavioral tasks following 2-week housing in chambers under seasonally relevant photoperiod extremes...
February 27, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Francesca Romana Rizzo, Mauro Federici, Nicola Biagio Mercuri
An increase of extracellular dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine (MDMA). Although this drug has been reported to affect the DA uptake transporter (DAT), it might activate other mechanisms to regulate the outflow of DA in the brain. Our aim was to examine the overall effects of MDMA on the release of DA in the striatum. We studied the effect of MDMA on stimulus-evoked synaptic DA release in dorsal striatal slices of mice using in vitro amperometric techniques...
March 3, 2018: Neuroscience
Jee-Young Lee, Nicholas P Lao-Kaim, Jacopo Pasquini, Günther Deuschl, Nicola Pavese, Paola Piccini
BACKGROUND: s: Over recent years there have been some conflicting reports upon the role of pallidal dopaminergic denervation in rest tremor in Parkinson's disease. OBJECTIVES: To clarify this issue we analyzed the clinical and 123I-FP-CIT SPECT data of a large cohort of early Parkinson's disease patients enrolled in the PPMI study. METHODS: Pallidal and striatal dopamine transporter uptake ratios were calculated in 382 patients (120 no-tremor, 60 tremor-dominant, and 202 indeterminate) and 150 controls...
February 24, 2018: Parkinsonism & related Disorders
Patrick Neiens, Angela De Simone, Anna Ramershoven, Georg Höfner, Lars Allmendinger, Klaus T Wanner
MS Binding Assays represent a label free alternative to radioligand binding assays. In this study, we present an LC-ESI-MS/MS method for the quantification of (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84, (R,R)-1), (S,S)-reboxetine ((S,S)-2), and (S)-citalopram ((S)-3) employed as highly selective nonlabelled reporter ligands in MS Binding Assays addressing the dopamine (DAT, (R,R)-D-84), the norepinephrine (NET, (S,S)-reboxetine), and the serotonin transporter (SERT, (S)-citalopram), respectively...
March 3, 2018: Biomedical Chromatography: BMC
Tayyabah Yousaf, Gennaro Pagano, Flavia Niccolini, Marios Politis
OBJECTIVES/BACKGROUND: Excessive daytime sleepiness (EDS) is a common disorder, which can manifest in isolation or in combination with other neurological or psychiatric disorders. We know relatively little about the mechanisms underlying the development of EDS and the clinical management of patients with EDS remains an unmet need. In this study, we hypothesised that thalamic dopaminergic function would be altered in subjects with EDS and we sought to investigate this by assessing [123 I]FP-CIT Single Photon Emission Computed Tomography (SPECT) data, which is a molecular imaging marker of dopamine transporter (DAT)...
March 2018: Sleep Medicine
Sabine Hellwig, Lars Frings, Annette Masuch, Werner Vach, Katharina Domschke, Claus Normann, Philipp T Meyer
We investigated if sleep deprivation (SD) and electroconvulsive therapy (ECT) affect striatal dopamine transporter (DAT) availability assessed by single-photon emission computed tomography (SPECT) and123 I-FP-CIT, if dopamine transporter gene (SLC6A3; DAT) variation modifies aforementioned parameters, and if SD response or SD-induced DAT changes correlate with ECT response. Sixteen patients with major depression (MDD) referred for ECT and 12 matched controls were prospectively recruited for imaging and SLC6A3 VNTR genotyping...
February 23, 2018: Journal of Neural Transmission
Shasha Xu, Shaoang Tu, Jinlong Gao, Jia Liu, Zhirui Guo, Jinming Zhang, Xingdang Liu, Jianhui Liang, Yiyun Huang, Mei Han
BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function...
February 23, 2018: BMC Complementary and Alternative Medicine
Natalia Moreno-Galarza, Liliana Mendieta, Victoria Palafox-Sánchez, Mireia Herrando-Grabulosa, Carles Gil, Daniel I Limón, José Aguilera
Several studies have shown that intrastriatal application of 1-methyl-4-phenylpyridinium (MPP+ ) produces similar biochemical changes in rat to those seen in Parkinson's disease (PD), such as dopaminergic terminal degeneration and consequent appearance of motor deficits, making the MPP+ lesion a widely used model of parkinsonism in rodents. Previous results from our group have shown a neuroprotective effect of the carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) under different types of stress...
February 19, 2018: Neurotoxicity Research
Sarah E Maggio, Meredith A Saunders, Thomas A Baxter, Kimberly Nixon, Mark A Prendergast, Guangrong Zheng, Peter Crooks, Linda P Dwoskin, Rachel D Slack, Amy H Newman, Richard L Bell, Michael T Bardo
RATIONALE: Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. OBJECTIVES: Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs...
February 18, 2018: Psychopharmacology
Yasunori Mito, Ichiro Yabe, Hiroaki Yaguchi, Toshiki Takei, Satoshi Terae, Yasutaka Tajima
OBJECTIVES: The aim of the present study was to determine the relation of urinary dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naïve patients with Parkinson's disease (PD). We therefore examined the relation of overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon emission computed tomography (123 I-FP-CIT SPECT)...
February 9, 2018: Parkinsonism & related Disorders
Motoyasu Honma, Yuri Masaoka, Takeshi Kuroda, Akinori Futamura, Azusa Shiromaru, Masahiko Izumizaki, Mitsuru Kawamura
OBJECTIVE: To determine whether Parkinson disease (PD) affects cross-modal function of vision and olfaction because it is known that PD impairs various cognitive functions, including olfaction. METHODS: We conducted behavioral experiments to identify the influence of PD on cross-modal function by contrasting patient performance with age-matched normal controls (NCs). We showed visual effects on the strength and preference of odor by manipulating semantic connections between picture/odorant pairs...
February 7, 2018: Neurology
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