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https://www.readbyqxmd.com/read/29138490/bidirectional-modulation-of-hippocampal-synaptic-plasticity-by-dopaminergic-d4-receptors-in-the-ca1-area-of-hippocampus
#1
Sheeja Navakkode, Katherine C M Chew, Sabrina Jia Ning Tay, Qingshu Lin, Thomas Behnisch, Tuck Wah Soong
Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119585/effects-of-dopamine-receptor-antagonist-antipsychotic-therapy-on-blood-pressure
#2
REVIEW
N H Gonsai, V H Amin, C G Mendpara, R Speth, G M Hale
WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist...
November 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29106549/the-in-vitro-actions-of-loxapine-on-dopaminergic-and-serotonergic-receptors-time-to-consider-atypical-classification-of-this-antipsychotic-drug
#3
Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, Pierre-Michel Llorca
Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Method: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [ 11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145 and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29101232/isopeptide-and-ester-bond-ubiquitination-both-regulate-degradation-of-the-human-dopamine-receptor-4
#4
Jennifer C Peeler, Sophia Schedin-Weiss, Mariluz Soula, Manija A Kazmi, Thomas P Sakmar
How an optimal level of human dopamine D4 receptor (hD4R) is maintained in synaptic membranes is not known. We show here that hD4R is ubiquitinated in primary neurons. We go on to show that ubiquitin is attached to hD4R through isopeptide and ester bonds. When lysine (Lys) residues of the hD4R are substituted with arginine (Arg) residues, cellular D4R protein levels increase. A synergistic effect on D4R levels is noted when cytoplasmic serine (Ser) and threonine (Thr) residues are mutated. Chloroquine, an inhibitor of lysosomal degradation, did not have an effect on hD4R protein levels...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29095852/neuronal-correlates-of-ketamine-and-walking-induced-gamma-oscillations-in-the-medial-prefrontal-cortex-and-mediodorsal-thalamus
#5
Katrina E Furth, Alex J McCoy, Caroline Dodge, Judith R Walters, Andres Buonanno, Claire Delaville
Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus...
2017: PloS One
https://www.readbyqxmd.com/read/29054088/the-interactions-among-organophosphate-pesticide-exposure-oxidative-stress-and-genetic-polymorphisms-of-dopamine-receptor-d4-increase-the-risk-of-attention-deficit-hyperactivity-disorder-in-children
#6
Chia-Huang Chang, Ching-Jung Yu, Jung-Chieh Du, Hsien-Chih Chiou, Hsin-Chang Chen, Winnie Yang, Ming-Yi Chung, Ying-Sheue Chen, Betau Hwang, I-Fang Mao, Mei-Lien Chen
OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified...
October 17, 2017: Environmental Research
https://www.readbyqxmd.com/read/29051383/d4-dopamine-receptor-high-resolution-structures-enable-the-discovery-of-selective-agonists
#7
Sheng Wang, Daniel Wacker, Anat Levit, Tao Che, Robin M Betz, John D McCorvy, A J Venkatakrishnan, Xi-Ping Huang, Ron O Dror, Brian K Shoichet, Bryan L Roth
Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D4 dopamine receptor...
October 20, 2017: Science
https://www.readbyqxmd.com/read/29046641/buspirone-counteracts-mk-801-induced-schizophrenia-like-phenotypes-through-dopamine-d3-receptor-blockade
#8
Sebastiano Alfio Torrisi, Salvatore Salomone, Federica Geraci, Filippo Caraci, Claudio Bucolo, Filippo Drago, Gian Marco Leggio
Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29017837/robo-ig4-is-a-dimerization-domain
#9
Galit Yom-Tov, Reut Barak, Omri Matalon, Mira Barda-Saad, Julia Guez-Haddad, Yarden Opatowsky
Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling...
October 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28993814/a-dopamine-receptor-genetic-variant-enhances-perceptual-speed-in-cognitive-healthy-subjects
#10
S Barral, C Habeck, E Gazes, P L De Jager, D A Bennett, Y Stern
Cognition is under strong genetic control, yet the specific genes are unknown. To investigate genetic influences on specific cognitive domains, 153 cognitive healthy subjects of European ancestry from the Reference Abilities Study (RANN) were genotyped for 1,160 variants within 446 neuropsychiatric genes. Adjusted linear regression models evaluated the association between the genetic variants and four reference abilities, which capture variance in age-related cognitive function (Vocabulary, Episodic Memory, Perceptual Speed, and Reasoning)...
June 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28975698/dopamine-d4-receptor-activation-restores-ca1-ltp-in-hippocampal-slices-from-aged-mice
#11
Fangli Guo, Jianhua Zhao, Dandan Zhao, Jiangang Wang, Xiaofang Wang, Zhiwei Feng, Martin Vreugdenhil, Chengbiao Lu
Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long-term potentiation (LTP) of the CA3-to-CA1 synapse. Age-related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca(2+) source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired...
October 3, 2017: Aging Cell
https://www.readbyqxmd.com/read/28948862/interaction-between-central-gabaa-receptor-and-dopaminergic-system-on-food-intake-in-neonatal-chicks-role-of-d1-and-gabaa-receptors
#12
Mona Hashemzadeh, Morteza Zendehdel, Vahab Babapour, Negar Panahi
OBJECTIVE: The present study designed to examine the role of central GABAA receptors and dopaminergic system on feeding behavior in neonatal layer-type chicken. METHODS: In this study, 6 experiments designed, each with 4 treatment groups (n = 44 in each experiment). In experiment 1, four groups of FD3 chicks received a dose of either the ICV injection of (A) control solution, (B) L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), (C) Gaboxadol (GABAA receptor agonist, 0...
September 26, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28948080/interaction-effects-of-git1-and-drd4-gene-variants-on-continuous-performance-test-variables-in-patients-with-adhd
#13
Hyojin Kim, Johanna Inhyang Kim, Haebin Kim, Jae-Won Kim, Bung-Nyun Kim
INTRODUCTION: The G protein-coupled receptor kinase interacting protein 1 gene (GIT1) has been proposed to be a risk gene for attention deficit hyperactivity disorder (ADHD), and it regulates the endocytosis of G protein-coupled receptors like dopamine receptors. The purpose of this study was to investigate the interaction effects of GIT1 and dopamine receptor D4 (DRD4) gene variants on variables of the continuous performance test (CPT). METHODS: This study recruited 255 ADHD patients and 98 healthy controls (HC) who underwent CPT and genetic analyses...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28940477/camp-levels-in-lymphocytes-and-cd4-regulatory-t-cell-functions-are-affected-by-dopamine-receptor-gene-polymorphisms
#14
Marco Cosentino, Natasa Kustrimovic, Marco Ferrari, Emanuela Rasini, Franca Marino
The neurotransmitter dopamine (DA) has prominent effects in the immune system and between the immune cells, CD4+ regulatory T lymphocytes (Treg), a specialized T cell subsets crucial for the control of immune homeostasis, are especially sensitive to DA. Dopaminergic receptors (DR) are grouped into two families according to their pharmacological profile and main second messenger coupling: the D1 -like (D1 and D5 ) which activate adenylate cyclase and the D2 -like (D2 , D3 and D4 ) which inhibit adenylate cyclase and exist in several variants, which have been associated to clinical conditions such as schizophrenia, bipolar disorder, substance abuse and addiction...
September 20, 2017: Immunology
https://www.readbyqxmd.com/read/28926158/selection-on-a-behaviour-related-gene-during-the-first-stages-of-the-biological-invasion-pathway
#15
Jakob C Mueller, Pim Edelaar, Adrián Baños-Villalba, Martina Carrete, Jaime Potti, Julio Blas, Jose Luis Tella, Bart Kempenaers
Human-induced biological invasions are common worldwide and often have negative impacts on wildlife and human societies. Several studies have shown evidence for selection on invaders after introduction to the new range. However, selective processes already acting prior to introduction have been largely neglected. Here, we tested whether such early selection acts on known behaviour-related gene variants in the yellow-crowned bishop (Euplectes afer), a pet-traded African songbird. We tested for nonrandom allele frequency changes after trapping, acclimation and survival in captivity...
September 19, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28900390/genetically-driven-enhancement-of-dopaminergic-transmission-affects-moral-acceptability-in-females-but-not-in-males-a-pilot-study
#16
Silvia Pellegrini, Sara Palumbo, Caterina Iofrida, Erika Melissari, Giuseppina Rota, Veronica Mariotti, Teresa Anastasio, Andrea Manfrinati, Rino Rumiati, Lorella Lotto, Michela Sarlo, Pietro Pietrini
Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28876518/externalizing-problem-behavior-in-adolescence-parenting-interacting-with-dat1-and-drd4-genes
#17
Annelies Janssens, Wim Van Den Noortgate, Luc Goossens, Hilde Colpin, Karine Verschueren, Stephan Claes, Karla Van Leeuwen
This study extends previous gene-by-environment (G × E) research through design and methodological advances and examines alternative hypotheses of diathesis stress, vantage sensitivity, and differential susceptibility. In a sample of 984 adolescents and their parents, we examined whether effects of parental support, proactive, punitive, harsh punitive, and psychological control on externalizing problem behavior are moderated by adolescents' genotype for the dopamine transporter (DAT1) or receptor D4 (DRD4) gene...
June 2017: Journal of Research on Adolescence: the Official Journal of the Society for Research on Adolescence
https://www.readbyqxmd.com/read/28874544/single-rat-muscle-na-channel-mutation-confers-batrachotoxin-autoresistance-found-in-poison-dart-frog-phyllobates-terribilis
#18
Sho-Ya Wang, Ging Kuo Wang
Poison-dart Phyllobates terribilis frogs sequester lethal amounts of steroidal alkaloid batrachotoxin (BTX) in their skin as a defense mechanism against predators. BTX targets voltage-gated Na(+) channels and enables them to open persistently. How BTX autoresistance arises in such frogs remains a mystery. The BTX receptor has been delineated along the Na(+) channel inner cavity, which is formed jointly by four S6 transmembrane segments from domains D1 to D4. Within the P. terribilis muscle Na(+) channel, five amino acid (AA) substitutions have been identified at D1/S6 and D4/S6...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28828402/neuregulin-and-dopamine-d4-receptors-contribute-independently-to-depotentiation-of-schaffer-collateral-ltp-by-temperoammonic-path-stimulation
#19
Yukitoshi Izumi, Charles F Zorumski
Prior studies have found that dopamine (DA), acting at D4 receptors, and neuregulin (NRG), likely acting at ErbB4 receptors, are involved in a form of depotentiation of long-term potentiation (LTP) at Schaffer collateral (SC) synapses in the hippocampus. Furthermore, DA and NRG actions are intertwined in that NRG induces DA release. We previously found that low-frequency stimulation (LFS) of temperoammonic (TA) inputs to area CA1 also depotentiates previously established SC LTP through a complex signaling pathway involving endocannabinoids, GABA, adenosine, and mitogen-activated protein kinases (MAPKs), but not glutamate...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28814511/targeting-phospholipase-d4-attenuates-kidney-fibrosis
#20
Priyanka Trivedi, Ramya K Kumar, Ashwin Iyer, Sarah Boswell, Casimiro Gerarduzzi, Vivekkumar P Dadhania, Zach Herbert, Nikita Joshi, James P Luyendyk, Benjamin D Humphreys, Vishal S Vaidya
Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury...
August 16, 2017: Journal of the American Society of Nephrology: JASN
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