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https://www.readbyqxmd.com/read/28649615/imaging-parkinson-s-disease-below-the-neck
#1
Per Borghammer, Karoline Knudsen, Tatyana D Fedorova, David J Brooks
Parkinson's disease is a systemic disorder with widespread and early α-synuclein pathology in the autonomic and enteric nervous systems, which is present throughout the gastrointestinal canal prior to diagnosis. Gastrointestinal and genitourinary autonomic symptoms often predate clinical diagnosis by several years. It has been hypothesized that progressive α-synuclein aggregation is initiated in hyperbranched, non-myelinated neuron terminals, and may subsequently spread via retrograde axonal transport. This would explain why autonomic nerves are so prone to formation of α-synuclein pathology...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28647012/striatal-activation-predicts-differential-therapeutic-responses-to-methylphenidate-and-atomoxetine
#2
Kurt P Schulz, Anne-Claude V Bédard, Jin Fan, Thomas B Hildebrandt, Mark A Stein, Iliyan Ivanov, Jeffrey M Halperin, Jeffrey H Newcorn
OBJECTIVE: Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). METHOD: A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design...
July 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28646469/the-cathinones-mdpv-and-%C3%AE-pvp-elicit-different-behavioral-and-molecular-effects-following-acute-exposure
#3
Giuseppe Giannotti, Isabella Canazza, Lucia Caffino, Sabrine Bilel, Andrea Ossato, Fabio Fumagalli, Matteo Marti
Since the mid-to-late 2000s, synthetic cathinones have gained popularity among drug users due to their psychostimulant effects greater than those produced by cocaine and amphetamine. Among them, 3,4-methylenedioxypyrovalerone (MDPV) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP) are ones of the most popular cathinones available in the clandestine market as "bath salts" or "fertilizers." Pre-clinical studies indicate that MDPV and α-PVP induced psychomotor stimulation, affected thermoregulation, and promoted reinforcing properties in rodents...
June 23, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28645061/the-neurochemical-consequences-of-methamphetamine-self-administration-in-male-and-female-rats
#4
Andrew Johansen, Lisa M McFadden
BACKGROUND: Methamphetamine (METH) is an addictive substance that is used in both males and females. Few preclinical studies have focused on understanding sex-differences in the neurochemical consequences of contingent METH. The purpose of the current study was to investigate potential sex-differences in the neurochemical consequences of METH self-administration. METHODS: Male and female adult rats were given extended access to METH or saline self-administration for 7d...
June 6, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28644892/r-modafinil-exerts-weak-effects-on-spatial-memory-acquisition-and-dentate-gyrus-synaptic-plasticity
#5
Bharanidharan Shanmugasundaram, Yogesh D Aher, Jana Aradska, Marija Ilic, Daniel Daba Feyissa, Predrag Kalaba, Nilima Y Aher, Vladimir Dragacevic, Babak Saber Marouf, Thierry Langer, Harald H Sitte, Harald Hoeger, Gert Lubec, Volker Korz
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28639878/exploring-the-phenotype-in-mild-cognitive-impairment-to-aid-the-prediction-of-those-at-risk-of-transitioning-to-parkinson-disease-and-dementia-with-lewy-bodies
#6
Jennifer Y Y Szeto, Glenda M Halliday, Sharon L Naismith, Simon J G Lewis
To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towards a longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition...
July 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28638597/rest-tremor-revisited-parkinson-s-disease-and-other-disorders
#7
REVIEW
Wei Chen, Franziska Hopfner, Jos Steffen Becktepe, Günther Deuschl
Tremor is the most common movement disorder characterized by a rhythmical, involuntary oscillatory movement of a body part. Since distinct diseases can cause similar tremor manifestations and vice-versa, it is challenging to make an accurate diagnosis. This applies particularly for tremor at rest. This entity was only rarely studied in the past, although a multitude of clinical studies on prevalence and clinical features of tremor in Parkinson's disease (PD), essential tremor and dystonia, have been carried out...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28637871/phosphorylation-at-serine-31-targets-tyrosine-hydroxylase-to-vesicles-for-transport-along-microtubules
#8
Ana Jorge-Finnigan, Rune Kleppe, Kunwar Jung-Kc, Ming Ying, Michael Marie, Ivan Rios-Mondragon, Michael F Salvatore, Jaakko Saraste, Aurora Martinez
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-Dopa, which is the rate-limiting step in the synthesis of catecholamines, particularly dopamine in dopaminergergic neurons. Low dopamine levels and death of the dopaminergic neurons are hallmarks of Parkinson's disease (PD), where α-synuclein is also a key player. TH is highly regulated, notably by phosphorylation of several Ser/Thr residues in the N-terminal tail. However, the functional role of TH phosphorylation at the Ser31 site (THpSer31) remains unclear...
June 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28633499/lateralized-basal-ganglia-vulnerability-to-pesticide-exposure-in-asymptomatic-agricultural-workers
#9
Mechelle M Lewis, Nicholas W Sterling, Guangwei Du, Eun-Young Lee, Grace Shyu, Michael Goldenberg, Thomas Allen, Christy Stetter, Lan Kong, Shedra Amy Snipes, Byron C Jones, Honglei Chen, Richard B Mailman, Xuemei Huang
Background: Pesticide exposure is linked to Parkinson's disease (PD), a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticide-exposed agricultural workers (AW) have nigral diffusion tensor (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28632695/serum-ceruloplasmin-and-striatal-dopamine-transporter-density-in-parkinson-disease-comparison-with-123i-fp-cit-spect
#10
Yoo Sung Song, Jong-Min Kim, Kyeong Joon Kim, Ji Young Yun, Sang Eun Kim
PURPOSE: In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin-along with its related serum markers- and striatal presynaptic dopaminergic denervation measured with I-FP-CIT SPECT. METHODS: We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism)...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28632692/improved-123i-ioflupane-binding-after-immunotherapy-in-anti-nae-antibody-positive-hashimoto-encephalopathy-that-clinically-mimicked-multiple-system-atrophy
#11
Juuri Otsuka, Ayumi Hida, Kamiyu Ogyu, Ryogo Minamimoto, Sousuke Takeuchi
We describe an 84-year-old man with anti-NH2-terminal of α-enolase antibody-positive Hashimoto encephalopathy that clinically mimicked multiple system atrophy who underwent investigation by dopamine transporter SPECT before and after immunotherapy. Before treatment, dopamine transporter SPECT showed reduced striatal I-ioflupane binding, with a mean specific binding ratio of 2.42, even though he had no apparent parkinsonism. After immunotherapy, mean specific binding ratio was improved to 3.22. Dopamine transporter SPECT was useful in this case to detect subclinical striatal dysfunction, and evaluation both before and after immunotherapy helped to distinguish between neurodegenerative disease and neuroimmunological disorder...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28631404/structural-connectivity-differences-in-motor-network-between-tremor-dominant-and-nontremor-parkinson-s-disease
#12
Gaetano Barbagallo, Maria Eugenia Caligiuri, Gennarina Arabia, Andrea Cherubini, Angela Lupo, Rita Nisticò, Maria Salsone, Fabiana Novellino, Maurizio Morelli, Giuseppe Lucio Cascini, Domenico Galea, Aldo Quattrone
Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI...
June 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28630892/disruption-of-the-axonal-trafficking-of-tyrosine-hydroxylase-mrna-impairs-catecholamine-biosynthesis-in-the-axons-of-sympathetic-neurons
#13
Armaz Aschrafi, Anthony E Gioio, Lijin Dong, Barry B Kaplan
Tyrosine hydroxylase (TH) is the enzyme that catalyzes the rate-limiting step in the biosynthesis of the catecholamine neurotransmitters. In a previous communication, evidence was provided that TH mRNA is trafficked to the axon, where it is locally translated. In addition, a 50-bp sequence element in the 3'untranslated region (3'UTR) of TH mRNA was identified that directs TH mRNA to distal axons (i.e., zip-code). In the present study, the hypothesis was tested that local translation of TH plays an important role in the biosynthesis of the catecholamine neurotransmitters in the axon and/or presynaptic nerve terminal...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28629580/folding-underlies-bidirectional-role-of-gpr37-pael-r-in-parkinson-disease
#14
REVIEW
Lina Leinartaité, Per Svenningsson
Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons...
June 16, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28627368/photoactivation-of-erk-creb-vmat2-pathway-attenuates-mpp-induced-neuronal-injury-in-a-cellular-model-of-parkinson-s-disease
#15
Xiaotong Gu, Lei Liu, Qi Shen, Da Xing
The vesicular monoamine transporter 2 (VMAT2) pumps dopamine from cytoplasm into synaptic vesicles for subsequent release, and the deficits of VMAT2 has been implicated in the dopaminergic neuronal cell loss which is considered as a typical pathological feature of Parkinson's disease (PD). Low-power laser irradiation (LPLI), a potent noninvasive physiotherapy approach, is capable of penetrating into nerve tissue to exert beneficial effects such as promoting nerve regeneration and ATP production. In the present study, we demonstrated that LPLI protects against MPP(+)-induced neurotoxicity via upregulation of VMAT2 in SH-SY5Y human dopaminergic neuroblastoma cells...
June 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28625719/atypical-dopamine-transporter-inhibitors-r-modafinil-and-jhw-007-differentially-affect-d2-autoreceptor-neurotransmission-and-the-firing-rate-of-midbrain-dopamine-neurons
#16
Alicia J Avelar, J Cao, Amy Hauck Newman, Michael J Beckstead
Abuse of psychostimulants like cocaine that inhibit dopamine (DA) reuptake through the dopamine transporter (DAT) represents a major public health issue, however FDA-approved pharmacotherapies have yet to be developed. Recently a class of ligands termed "atypical DAT inhibitors" has gained attention due to their range of effectiveness in increasing extracellular dopamine (DA) levels without demonstrating significant abuse liability. These compounds not only hold promise as therapeutic agents to treat stimulant use disorders but also as experimental tools to improve our understanding of DAT function...
June 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28625517/reduced-tdp-43-expression-improves-neuronal-activities-in-a-drosophila-model-of-perry-syndrome
#17
Yuka Hosaka, Tsuyoshi Inoshita, Kahori Shiba-Fukushima, Changxu Cui, Taku Arano, Yuzuru Imai, Nobutaka Hattori
Parkinsonian Perry syndrome, involving mutations in the dynein motor component dynactin or p150(Glued), is characterized by TDP-43 pathology in affected brain regions, including the substantia nigra. However, the molecular relationship between p150(Glued) and TDP-43 is largely unknown. Here, we report that a reduction in TDP-43 protein levels alleviates the synaptic defects of neurons expressing the Perry mutant p150(G50R) in Drosophila. Dopaminergic expression of p150(G50R), which decreases dopamine release, disrupts motor ability and reduces the lifespan of Drosophila...
June 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28623807/hiv-tat-excites-d1-receptor-like-expressing-neurons-from-rat-nucleus-accumbens
#18
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca(2+) homeostasis of NAcc neurons...
June 8, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28623359/allosteric-modulatory-effects-of-sri-20041-and-sri-30827-on-cocaine-and-hiv-1-tat-protein-binding-to-human-dopamine-transporter
#19
Wei-Lun Sun, Pamela M Quizon, Yaxia Yuan, Wei Zhang, Subramaniam Ananthan, Chang-Guo Zhan, Jun Zhu
Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622913/targeting-urate-to-reduce-oxidative-stress-in-parkinson-disease
#20
REVIEW
Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants...
June 13, 2017: Experimental Neurology
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