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https://www.readbyqxmd.com/read/29908325/dopamine-d2-receptor-activation-potently-inhibits-striatal-glutamatergic-transmission-in-a-g2019s-lrrk2-genetic-model-of-parkinson-s-disease
#1
Alessandro Tozzi, Valentina Durante, Guendalina Bastioli, Petra Mazzocchetti, Salvatore Novello, Alessandro Mechelli, Michele Morari, Cinzia Costa, Andrea Mancini, Massimiliano Di Filippo, Paolo Calabresi
Among genetic abnormalities identified in Parkinson's disease (PD), mutations of the leucine-rich repeat kinase2 (LRRK2) gene, such as the G2019S missense mutation linked to enhanced kinase activity, are the most common. While the complex role of LRRK2 has not been fully elucidated, evidence that mutated kinase activity affects synaptic transmission has been reported. Thus, our aim was to explore possible early alterations of neurotransmission produced by the G2019S LRRK2 mutation in PD. We performed electrophysiological patch-clamp recordings of striatal spiny projection neurons (SPNs) in the G2019S-Lrrk2 knock-in (KI) mouse model of PD, in D1994S kinase-dead (KD), Lrrk2 knock-out (KO) and wild-type (WT) mice...
June 13, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29908239/the-psychostimulant-%C3%A2-cis-4-4-dimethylaminorex-4-4-dmar-interacts-with-human-plasmalemmal-and-vesicular-monoamine-transporters
#2
Julian Maier, Felix P Mayer, Dino Luethi, Marion Holy, Kathrin Jäntsch, Harald Reither, Lena Hirtler, Marius C Hoener, Matthias E Liechti, Christian Pifl, Simon D Brandt, Harald H Sitte
(±)-cis-4,4'-Dimethylaminorex (4,4'-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effects of 4,4'-DMAR on human high-affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). In addition, we assessed its binding affinities to monoamine receptors and transporters. Furthermore, we investigated the interaction of 4,4'-DMAR with the vesicular monoamine transporter 2 (VMAT2) in rat phaeochromocytoma (PC12) cells and synaptic vesicles prepared from human striatum...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29908232/the-association-of-spinophilin-with-disks-large-associated-protein-3-sapap3-is-regulated-by-metabotropic-glutamate-receptor-mglur-5
#3
Cameron W Morris, Darryl S Watkins, Asma B Salek, Michael C Edler, Anthony J Baucum
Spinophilin is the most abundant protein phosphatase 1 targeting protein in the postsynaptic density of dendritic spines. Spinophilin associates with myriad synaptic proteins to regulate normal synaptic communication; however, the full complement of spinophilin interacting proteins and mechanisms regulating spinophilin interactions are unclear. Here we validate an association between spinophilin and the scaffolding protein, disks large-associated protein 3 (SAP90/PSD-95 associated protein 3; SAPAP3). Loss of SAPAP3 leads to obsessive-compulsive disorder (OCD)-like behaviors due to alterations in metabotropic glutamate receptor (mGluR) signaling...
June 13, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29907842/reward-representing-d1-type-neurons-in-the-medial-shell-of-the-accumbens-nucleus-regulate-palatable-food-intake
#4
Máté Durst, Katalin Könczöl, Tamás Balázsa, Mark D Eyre, Zsuzsanna E Tóth
BACKGROUND/OBJECTIVES: Dysfunction in reward-related aspects of feeding, and consequent overeating in humans, is a major contributor to obesity. Intrauterine undernutrition and overnutrition are among the predisposing factors, but the exact mechanism of how overeating develops is still unclear. Consummatory behavior is regulated by the medial shell (mSh) of the accumbens nucleus (Nac) through direct connections with the rostral part of the lateral hypothalamic area (LHA). Our aim was to investigate whether an altered Nac-LHA circuit may underlie hyperphagic behavior...
June 15, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29907754/nano-particle-mediated-inhibition-of-parkinson-s-disease-using-computational-biology-approach
#5
Aman Chandra Kaushik, Shiv Bharadwaj, Sanjay Kumar, Dong-Qing Wei
Parkinson's disease (PD) arises as neurodegenerative disorder and characterized by progressive deterioration of motor functions due to forfeiture of dopamine-releasing neurons. During PD, neurons at stake loss their functionality that results into cognition impairment and forgetfulness, commonly called as dementia. Recently, nanoparticles (NPs) have been reported for easy drug delivery through blood-brain barrier (BBB) into the central nervous system (CNS) against the conventional drug delivery systems. However, present study attempted to elucidate the α-synuclein activity, a major factor casing PD, in presence of its inhibitor cerium oxide (CeO2 ) nanoparticle via computational biology approach...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29907646/genetic-modifiers-of-neurodegeneration-in-a-drosophila-model-of-parkinson-s-disease
#6
Sierra Lavoy, Vinita G Chittoor-Vinod, Clement Y Chow, Ian Martin
Disease phenotypes can be highly variable among individuals with the same pathogenic mutation. There is increasing evidence that background genetic variation is a strong driver of disease variability in addition to the influence of environment. To understand the genotype-phenotype relationship that determines the expressivity of a pathogenic mutation, a large number of backgrounds must be studied. This can be efficiently achieved using model organism collections such as the Drosophila Genetic Reference Panel (DGRP)...
June 15, 2018: Genetics
https://www.readbyqxmd.com/read/29907594/repositioning-dopamine-d2-receptor-agonist-bromocriptine-to-enhance-docetaxel-chemotherapy-and-treat-bone-metastatic-prostate-cancer
#7
Yang Yang, Kenza Mamouni, Xin Li, Yanhua Chen, Sravan Kavuri, Yuhong Du, Haian Fu, Omer Kucuk, Daqing Wu
Docetaxel resistance remains a major obstacle in the treatment of prostate cancer (PCa) bone metastasis. In this study, we demonstrate that the dopamine D2 receptor (DRD2) agonist bromocriptine effectively enhances docetaxel efficacy and suppresses skeletal growth of PCa in preclinical models. DRD2 is ubiquitously expressed in PCa cell lines, and DRD2 is significantly reduced in PCa tissues with high Gleason score. Bromocriptine has weak to moderate cytotoxicity in PCa cells, but effectively induces cell cycle arrest...
June 15, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29907159/jnk-mediated-microglial-dicer-degradation-potentiates-inflammatory-responses-to-induce-dopaminergic-neuron-loss
#8
Qing Wang, Qian He, Yifei Chen, Wei Shao, Chao Yuan, Yizheng Wang
BACKGROUND: Amplified inflammation is important for the progression of Parkinson's disease (PD). However, how this enhanced inflammation is regulated remains largely unknown. Deletion of DICER leads to progressive dopamine neuronal loss and induces gliosis. We hypothesized that the homeostasis of microglial DICER would be responsible for the amplified inflammation in the mouse model of PD. METHODS: The microglia or C57BL/6 mice were treated or injected with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+ ), respectively, for the model establishment...
June 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29907085/long-term-persistence-of-withdrawal-of-temazepam-zopiclone-and-zolpidem-in-older-adults-a-3-year-follow-up-study
#9
Juha Puustinen, Ritva Lähteenmäki, Janne Nurminen, Tero Vahlberg, Pertti Aarnio, Markku Partinen, Ismo Räihä, Pertti J Neuvonen, Sirkka-Liisa Kivelä
BACKGROUND: Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. METHODS: 92 outpatients (≥55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9...
June 15, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/29906709/short-term-efficacy-and-tolerability-of-lurasidone-in-the-treatment-of-acute-schizophrenia-a-meta-analysis-of-randomized-controlled-trials
#10
REVIEW
Wei Zheng, Dong-Bin Cai, Xin-Hu Yang, Lu Li, Qing-E Zhang, Chee H Ng, Gabor S Ungvari, Xian-Bin Li, Yu-Ping Ning, Yu-Tao Xiang
BACKGROUND: Lurasidone, an azapirone derivative, is a novel second generation antipsychotic with potent binding affinity for dopamine D2, serotonin 5-HT2A , 5-HT7, 5-HT1A, and noradrenaline alpha2C receptors. This updated meta-analysis of randomized controlled trials (RCTs) examined the short-term efficacy and tolerability of lurasidone in the treatment of acute schizophrenia. METHODS: Double-blinded RCTs reporting on the short-term effects of lurasidone were included...
June 5, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29906101/dopamine-oxidation-products-as-mitochondrial-endotoxins-a-potential-molecular-mechanism-for-preferential-neurodegeneration-in-parkinson-disease
#11
Alice Biosa, Irene Arduini, Maria Eugenia Soriano, Valentina Giorgio, Paolo Bernardi, Marco Bisaglia, Luigi Bubacco
The preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta is responsible for the motor impairment associated with Parkinson's disease. Dopamine is a highly reactive molecule, which is usually stored inside synaptic vesicles where it is stabilized by the ambient low pH. However, free cytosolic dopamine can auto-oxidize, generating reactive oxygen species, and lead to the formation of toxic quinones. In the present work, we have analyzed the mechanisms through which the dysfunction of dopamine homeostasis could induce cell toxicity, by focusing in particular on the damage induced by dopamine oxidation products at the mitochondrial level...
June 15, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29905970/neurexin-superfamily-cell-membrane-receptor-contactin-associated-protein-like-4-cntnap4-is-involved-in-neural-egfl-like-1-nell-1-responsive-osteogenesis
#12
Chenshuang Li, Zhong Zheng, Pin Ha, Xiaoyan Chen, Wenlu Jiang, Shan Sun, Feng Chen, Greg Asatrian, Emily A Berthiaume, Jong Kil Kim, Eric C Chen, Shen Pang, Xinli Zhang, Kang Ting, Chia Soo
Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system...
June 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29905798/nicotine-induced-conditional-place-preference-is-affected-by-head-injury-correlation-with-dopamine-release-in-the-nucleus-accumbens-shell
#13
Chen Yuan-Hao, Tung-Tai Kuo, Eagle Yi-Kung Huang, Barry J Hoffer, Jen-Hsin Kao, Yu-Ching Chou, Yung-Hsiao Chiang, Jonathan Miller
Background: Traumatic brain injury (TBI) is known to impact dopamine-mediated reward pathways, but the underlying mechanisms have not been fully established. Methods: Nicotine-induced conditional place preference (CPP) was used to study rats exposed to a 6-psi fluid percussion injury (FPI) with and without prior exposure to nicotine. Preference was quantified as a score defined as (C1-C2) / (C1+C2), where C1 is time in the nicotine-paired compartment and C2 is time in the saline-paired compartment...
June 14, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29905542/the-features-of-the-women-s-simpathoadrenal-system-functional-state-with-risk-of-early-pregnancy-termination
#14
S Korovay
Preterm labor is an urgent medical-social and demographic issue at the present stage. A considerable number of factors affects the course of pregnancy and its outcome, their effect is realized at the level of the central nervous system through numerical metabolic interactions, where monoaminergic systems play an important role. Objective - to study the features of the sympathoadrenal system state by determining the excretion level of DOPHA, dopamine, norepinephrine and epinephrine in women's daily urine with different periods of abortion...
May 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29905488/effects-of-interaction-between-drd4-methylation-and-prenatal-maternal-stress-on-methylphenidate-induced-changes-in-continuous-performance-test-performance-in-youth-with-attention-deficit-hyperactivity-disorder
#15
Johanna Inhyang Kim, Jae-Won Kim, Inkyung Shin, Bung-Nyun Kim
OBJECTIVES: Environmental factors may interact with genetic factors via the epigenetic process, and this interaction can contribute to inter-individual variability in the treatment response. The purpose of this study was to investigate the interaction effects between dopamine receptor D4 (DRD4) methylation and prenatal maternal stress on the methylphenidate (MPH) response of youth with attention-deficit/hyperactivity disorder (ADHD). METHODS: This study was an 8-week open-label trial of MPH that included 74 ADHD youth...
June 15, 2018: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/29905019/i-123-datscan-spect-brain-imaging-in-parkinsonian-syndromes-utility-of-the-putamen-to-caudate-ratio
#16
Manuela Matesan, Santhosh Gaddikeri, Katelan Longfellow, Robert Miyaoka, Saeed Elojeimy, Shana Elman, Shu-Ching Hu, Satoshi Minoshima, David Lewis
BACKGROUND AND PURPOSE: Computer-based analysis of Dopamine transporter imaging (DaTscan) can aid in image interpretation. In this study, we examined the distribution of putamen-to-caudate ratios (PCRs) obtained by using a clinically available semiquantification method. METHODS: Medical records of 32 patients (M:16) with a diagnosis of Parkinson's disease (PD) (n = 22) or Parkinson's plus syndromes (PPS) (n = 10) based on clinical follow-up, were retrospectively reviewed...
June 14, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29904960/enhanced-dopamine-d2-autoreceptor-function-in-the-adult-prefrontal-cortex-contributes-to-dopamine-hypoactivity-following-adolescent-social-stress
#17
Matthew A Weber, Eric T Graack, Jamie L Scholl, Kenneth J Renner, Gina L Forster, Michael J Watt
Adult psychiatric disorders characterized by cognitive deficits reliant on prefrontal cortex (PFC) dopamine are promoted by teenage bullying. Similarly, male Sprague-Dawley rats exposed to social defeat in mid-adolescence (P35-39) show impaired working memory in adulthood (P56-70), along with decreased medial PFC (mPFC) dopamine activity that results in part from increased dopamine transporter-mediated clearance. Here, we determined if dopamine synthesis and D2 autoreceptor-mediated inhibition of dopamine release in the adult mPFC are also enhanced by adolescent defeat to contribute to later dopamine hypofunction...
June 14, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29904828/estrogen-migraine-and-vascular-risk
#18
Gianni Allais, Giulia Chiarle, Silvia Sinigaglia, Gisella Airola, Paola Schiapparelli, Chiara Benedetto
Migraine has a predilection for female sex and the course of symptoms is influenced by life stage (presence of menstrual cycle, pregnancy, puerperium, menopause) and use of hormone therapy, such as hormonal contraception and hormone replacement therapy. Hormonal changes figure among common migraine triggers, especially sudden estrogen drop. Moreover, estrogens can modulate neuronal excitability, through serotonin, norepinephrine, dopamine, and endorphin regulation, and they interact with the vascular endothelium of the brain...
June 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29904346/rhes-counteracts-dopamine-neuron-degeneration-and-neuroinflammation-depending-on-gender-and-age
#19
Giulia Costa, Annalisa Pinna, Pier Francesca Porceddu, Maria Antonietta Casu, Anna Di Maio, Francesco Napolitano, Alessandro Usiello, Micaela Morelli
We have recently shown that male Rhes knockout (KO) mice develop a mild form of spontaneous Parkinson's disease (PD)-like phenotype, characterized by motor impairment and a decrease in nigrostriatal dopamine (DA) neurons. Experimental evidence has implicated neuroinflammation in PD progression, and the presence of activated glial cells has been correlated with DA neuron degeneration. Despite this, several factors, such as gender, have been found to affect DAergic neuron degeneration and influence neuroinflammation, explaining the differences between men and women in the etiology of PD...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29904009/an-electrochemical-study-on-the-copolymer-formed-from-piperazine-and-aniline-monomers
#20
Samiha Dkhili, Sara López-Bernabeu, Chahineze Nawel Kedir, Francisco Huerta, Francisco Montilla, Salma Besbes-Hentati, Emilia Morallon
A study on the electrochemical oxidation of piperazine and its electrochemical copolymerization with aniline in acidic medium is presented. It was found that the homopolymerization of piperazine cannot be achieved under electrochemical conditions. A combination of electrochemistry, in situ Fourier transform infrared (FTIR), and ex situ X-ray photoelectron spectroscopy (XPS) spectroscopies was used to characterize both the chemical structure and the redox behavior of an electrochemically synthesized piperazine⁻aniline copolymer...
June 14, 2018: Materials
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