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DARPP-32

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https://www.readbyqxmd.com/read/29782621/darpp-32-and-t-darpp-promote-non-small-cell-lung-cancer-growth-through-regulation-of-ikk%C3%AE-dependent-cell-migration
#1
Sk Kayum Alam, Matteo Astone, Ping Liu, Stephanie R Hall, Abbygail M Coyle, Erin N Dankert, Dane K Hoffman, Wei Zhang, Rui Kuang, Anja C Roden, Aaron S Mansfield, Luke H Hoeppner
Lung cancer is the leading cause of cancer-related death worldwide. Here we demonstrate that elevated expression of dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32) and its truncated splice variant t-DARPP promote lung tumor growth, while abrogation of DARPP-32 expression in human non-small cell lung cancer (NSCLC) cells reduces tumor growth in orthotopic mouse models. We observe a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-α (IKKα) that promotes NSCLC cell migration through non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NF-κB2) signaling...
2018: Communications biology
https://www.readbyqxmd.com/read/29778803/age-affects-reinforcement-learning-through-dopamine-based-learning-imbalance-and-high-decision-noise-not-through-parkinsonian-mechanisms
#2
Ravi B Sojitra, Itamar Lerner, Jessica R Petok, Mark A Gluck
Probabilistic reinforcement learning declines in healthy cognitive aging. While some findings suggest impairments are especially conspicuous in learning from rewards, resembling deficits in Parkinson's disease, others also show impairments in learning from punishments. To reconcile these findings, we tested 252 adults from 3 age groups on a probabilistic reinforcement learning task, analyzed trial-by-trial performance with a Q-reinforcement learning model, and correlated both fitted model parameters and behavior to polymorphisms in dopamine-related genes...
April 19, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29731676/genetic-ablation-of-ews-rna-binding-protein-1-ewsr1-leads-to-neuroanatomical-changes-and-motor-dysfunction-in-mice
#3
Yeojun Yoon, Hasang Park, Sangyeon Kim, Phuong T Nguyen, Seung Jae Hyeon, Sooyoung Chung, Hyeonjoo Im, Junghee Lee, Sean Bong Lee, Hoon Ryu
A recent study reveals that missense mutations of EWSR1 are associated with neurodegenerative disorders such as amyotrophic lateral sclerosis, but the function of wild-type (WT) EWSR1 in the central nervous system (CNS) is not known yet. Herein, we investigated the neuroanatomical and motor function changes in Ewsr1 knock out (KO) mice. First, we quantified neuronal nucleus size in the motor cortex, dorsal striatum and hippocampus of three different groups: WT, heterozygous Ewsr1 KO (+/-), and homozygous Ewsr1 KO (-/-) mice...
April 2018: Experimental Neurobiology
https://www.readbyqxmd.com/read/29729893/memantine-ameliorates-depressive-like-behaviors-by-regulating-hippocampal-cell-proliferation-and-neuroprotection-in-olfactory-bulbectomized-mice
#4
Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Shogo Kadota, Jinichi Isono, Takayo Odaira, Wakana Sakuma, Yuichiro Arai, Takeshi Tadano, Koichi Tan-No
Our previous study suggested that the non-competitive N-methyl-d-aspartate receptor antagonist memantine (MEM) inhibits dopamine (DA) reuptake and turnover by inhibiting brain monoamine oxidase. Clinical studies have reported that MEM may improve depressive symptoms; however, specific mechanisms underlying this effect are unclear. We performed emotional behavior, tail suspension, and forced swimming tests to examine whether MEM has antidepressant effects in olfactory bulbectomized (OBX) mice, an animal model of depression...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29709465/huntington-s-disease-pattern-of-transcriptional-dysregulation-in-the-absence-of-mutant-huntingtin-is-produced-by-knockout-of-neuronal-glt-1
#5
Robert B Laprairie, Geraldine T Petr, Yan Sun, Kathryn D Fischer, Eileen M Denovan-Wright, Paul A Rosenberg
GLT-1 is the major glutamate transporter in the brain, and is expressed in astrocytes and in axon terminals in the hippocampus, cortex, and striatum. Neuronal GLT-1 accounts for only 5-10% of total brain GLT-1 protein, and its function is uncertain. In HD, synaptic dysfunction of the corticostriate synapse is well-established. Transcriptional dysregulation is a key feature of HD. We hypothesized that deletion of neuronal GLT-1, because it is expressed in axon terminals in the striatum, might produce a synaptopathy similar to that present in HD...
April 27, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29627696/effects-of-the-141c-insertion-deletion-polymorphism-in-the-dopamine-d2-receptor-gene-on-the-dopamine-system-in-the-striatum-in-patients-with-schizophrenia
#6
Junya Matsumoto, Atsuko Nagaoka, Yasuto Kunii, Itaru Miura, Mizuki Hino, Shin-Ichi Niwa, Hiroyuki Nawa, Hitoshi Takahashi, Akiyoshi Kakita, Hirooki Yabe
The relationships between -141C insertion/deletion (Ins/Del) polymorphisms in the dopamine D2 receptor gene and the two dopamine system integrators, i.e., dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN), are still unclear. In this study, we assessed the effect of this polymorphism on DARPP-32 and CaN protein expression in the postmortem striatum of patients with schizophrenia and control individuals. The expression levels of truncated DARPP and CaN were lower in Del allele carriers...
March 29, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29480209/httq111-huntington-s-disease-knock-in-mice-exhibit-brain-region-specific-morphological-changes-and-synaptic-dysfunction
#7
Marina Kovalenko, Austen Milnerwood, James Giordano, Jason St Claire, Jolene R Guide, Mary Stromberg, Tammy Gillis, Ellen Sapp, Marian DiFiglia, Marcy E MacDonald, Jeffrey B Carroll, Jong-Min Lee, Susan Tappan, Lynn Raymond, Vanessa C Wheeler
BACKGROUND: Successful disease-modifying therapy for Huntington's disease (HD) will require therapeutic intervention early in the pathogenic process. Achieving this goal requires identifying phenotypes that are proximal to the HTT CAG repeat expansion. OBJECTIVE: To use Htt CAG knock-in mice, precise genetic replicas of the HTT mutation in patients, as models to study proximal disease events. METHODS: Using cohorts of B6J.HttQ111/+ mice from 2 to 18 months of age, we analyzed pathological markers, including immunohistochemistry, brain regional volumes and cortical thickness, CAG instability, electron microscopy of striatal synapses, and acute slice electrophysiology to record glutamatergic transmission at striatal synapses...
2018: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/29454746/phosphodiesterase-inhibition-and-modulation-of-corticostriatal-and-hippocampal-circuits-clinical-overview-and-translational-considerations
#8
REVIEW
P R A Heckman, A Blokland, E P P Bollen, J Prickaerts
The corticostriatal and hippocampal circuits contribute to the neurobiological underpinnings of several neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease and schizophrenia. Based on biological function, these circuits can be clustered into motor circuits, associative/cognitive circuits and limbic circuits. Together, dysfunctions in these circuits produce the wide range of symptoms observed in related neuropsychiatric disorders. Intracellular signaling in these circuits is largely mediated through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway with an additional role for the cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG) pathway, both of which can be regulated by phosphodiesterase inhibitors (PDE inhibitors)...
April 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29410441/involvement-of-pka-darpp-32-pp1%C3%AE-and-%C3%AE-arrestin-akt-gsk-3%C3%AE-signaling-in-cadmium-induced-da-d2-receptor-mediated-motor-dysfunctions-protective-role-of-quercetin
#9
Richa Gupta, Rajendra K Shukla, Ankita Pandey, Tanuj Sharma, Yogesh K Dhuriya, Pranay Srivastava, Manjul P Singh, Mohammad Imran Siddiqi, Aditya B Pant, Vinay K Khanna
Given increasing risk of cadmium-induced neurotoxicity, the study was conducted to delineate the molecular mechanisms associated with cadmium-induced motor dysfunctions and identify targets that govern dopaminergic signaling in the brain involving in vivo, in vitro, and in silico approaches. Selective decrease in dopamine (DA)-D2 receptors on cadmium exposure was evident which affected the post-synaptic PKA/DARPP-32/PP1α and β-arrestin/Akt/GSK-3β signaling concurrently in rat corpus striatum and PC12 cells...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29408363/dopamine-depletion-shifts-behavior-from-activity-based-reinforcers-to-more-sedentary-ones-and-adenosine-receptor-antagonism-reverses-that-shift-relation-to-ventral-striatum-darpp32-phosphorylation-patterns
#10
Laura López-Cruz, Noemí San Miguel, Carla Carratalá-Ros, Lidón Monferrer, John D Salamone, Mercè Correa
The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A1 /A2A receptor antagonist, and in striatal areas DA D1 and D2 receptors are co-localized with adenosine A1 and A2A receptors respectively. In the present work, we evaluated the effect of caffeine on anergia induced by the VMAT-2 inhibitor tetrabenazine (TBZ), which depletes DA...
February 2, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29355642/calpastatin-ablation-aggravates-the-molecular-phenotype-in-cell-and-animal-models-of-huntington-disease
#11
Jonasz Jeremiasz Weber, Simon Johannes Kloock, Maike Nagel, Midea Malena Ortiz-Rios, Julian Hofmann, Olaf Riess, Huu Phuc Nguyen
Deciphering the molecular pathology of Huntington disease is of particular importance, not only for a better understanding of this neurodegenerative disease, but also to identify potential therapeutic targets. The polyglutamine-expanded disease protein huntingtin was shown to undergo proteolysis, which results in the accumulation of toxic and aggregation-prone fragments. Amongst several classes of proteolytic enzymes responsible for huntingtin processing, the group of calcium-activated calpains has been found to be a significant mediator of the disease protein toxicity...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29221855/toll-like-receptor-4-regulates-anxiety-like-behavior-and-darpp-32-phosphorylation
#12
T Femenia, Y Qian, T Arentsen, H Forssberg, R Diaz Heijtz
Toll-like receptors (TLRs) play a crucial role in early innate immune responses to inflammatory agents and pathogens. In the brain, some members of the TLR family are expressed in glial cells and neurons. In particular, TLR4 has been involved in learning and memory processes, stress-induced adaptations, and pathogenesis of neurodegenerative disorders. However, the role of TLR4 in emotional behaviors and their underlying mechanisms are poorly understood. In this study, we investigated the role of TLR4 in emotional and social behavior by using different behavioral approaches, and assessed potential molecular alterations in important brain areas involved in emotional responses...
December 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29209158/induced-pluripotent-stem-cell-derived-neural-stem-cell-transplantations-reduced-behavioral-deficits-and-ameliorated-neuropathological-changes-in-yac128-mouse-model-of-huntington-s-disease
#13
Abeer Al-Gharaibeh, Rebecca Culver, Andrew N Stewart, Bhairavi Srinageshwar, Kristin Spelde, Laura Frollo, Nivya Kolli, Darren Story, Leela Paladugu, Sarah Anwar, Andrew Crane, Robert Wyse, Panchanan Maiti, Gary L Dunbar, Julien Rossignol
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by neuronal loss and motor dysfunction. Although there is no effective treatment, stem cell transplantation offers a promising therapeutic strategy, but the safety and efficacy of this approach needs to be optimized. The purpose of this study was to test the potential of intra-striatal transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them into neural stem cells in vitro , labeled them with Hoechst, and transplanted them bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29161694/immunohistochemical-localization-of-darpp-32-in-the-brain-of-two-lungfishes-further-assessment-of-its-relationship-with-the-dopaminergic-system
#14
Jesús M López, Ruth Morona, Agustín González
The distribution of DARPP-32 (a phosphoprotein related to the dopamine D1 receptor) has been widely used as a means to clarify the brain regions with dopaminoceptive cells, primarily in representative species of tetrapods. The relationship between dopaminergic and dopaminoceptive elements is frequently analyzed using the catecholamine marker tyrosine hydroxylase (TH). In the present study, by means of combined immunohistochemistry, we have analyzed these relationships in lungfishes, the only group of sarcopterygian fishes represented by 6 extant species that are the phylogenetically closest living relatives of tetrapods...
2017: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/29107639/cjun-n-terminal-kinase-jnk-mediates-cortico-striatal-signaling-in-a-model-of-parkinson-s-disease
#15
Giada Spigolon, Anna Cavaccini, Massimo Trusel, Raffaella Tonini, Gilberto Fisone
The cJun N-terminal kinase (JNK) signaling pathway has been extensively studied with regard to its involvement in neurodegenerative processes, but little is known about its functions in neurotransmission. In a mouse model of Parkinson's disease (PD), we show that the pharmacological activation of dopamine D1 receptors (D1R) produces a large increase in JNK phosphorylation. This effect is secondary to dopamine depletion, and is restricted to the striatal projection neurons that innervate directly the output structures of the basal ganglia (dSPN)...
February 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29100151/aripiprazole-relieves-motivational-anhedonia-in-rats
#16
Simona Scheggi, Teresa Pelliccia, Carla Gambarana, Maria Graziella De Montis
BACKGROUND: Anhedonia is considered a relevant feature in depression and psychosis, characterized by poor treatment outcome, and associated with deficits in mesolimbic dopaminergic responsiveness. Clinical studies suggest the potential utility of aripiprazole as adjunctive therapy for resistant depression. Since aripiprazole can stabilize the dopaminergic system, in search of tailored therapeutic strategies for reward dysfunctions, we investigated whether the drug restored motivation toward positive stimuli in a rat model...
February 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29093677/levodopa-benserazide-loaded-microspheres-alleviate-l-dopa-induced-dyskinesia-through-preventing-the-over-expression-of-d1r-shp-2-erk1-2-signaling-pathway-in-a-rat-model-of-parkinson-s-disease
#17
Ying Wan, Na Wu, Lu Song, Xijin Wang, Zhenguo Liu, Weien Yuan, Jing Gan
Background: The long-term intermittent Levodopa (L-dopa) stimulation contributes to an aberrant activation of D1 receptor (D1R) mediated extracellular signal-regulated kinases1/2 (ERK1/2) in the striatal medium spiny neurons, resulting in the occurrence of L-dopa induced dyskinesia (LID). Recently, a novel signaling pathway, D1R/Shp-2/ERK1/2, was proposed to be required for the occurrence of LID. Here we designed the study in which two different methods of L-dopa delivery [continuous dopamine stimulation (CDS) vs...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29082320/%C3%AE-9-tetrahydrocannabinol-experience-influences-%C3%AE-fosb-and-downstream-gene-expression-in-prefrontal-cortex
#18
Matthew F Lazenka, Minho Kang, Dipanjana Datta De, Dana E Selley, Laura J Sim-Selley
Introduction: Repeated administration of abused drugs, including Δ9 -tetrahydrocannabinol (THC), induces the stable transcription factor ΔFosB in dopaminergic terminal field regions of the mesolimbic system. These studies investigated the effect of prior repeated THC treatment on THC-induced ΔFosB expression and regulation of downstream targets in the forebrain. Methods: Mice received THC (10 mg/kg) or vehicle twice daily for 13 days, and then half of each group received a single injection of THC or vehicle 45 min before brain collection...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29056363/pramipexole-reduces-soluble-mutant-huntingtin-and-protects-striatal-neurons-through-dopamine-d3-receptors-in-a-genetic-model-of-huntington-s-disease
#19
Diego Luis-Ravelo, Héctor Estévez-Silva, Pedro Barroso-Chinea, Domingo Afonso-Oramas, Josmar Salas-Hernández, Julia Rodríguez-Núñez, Abraham Acevedo-Arozena, Daniel Marcellino, Tomás González-Hernández
Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal expansion of the polyglutamine tract in the huntingtin protein (HTT). The toxicity of mutant HTT (mHTT) is associated with intermediate mHTT soluble oligomers that subsequently form intranuclear inclusions. Thus, interventions promoting the clearance of soluble mHTT are regarded as neuroprotective. Striatal neurons are particularly vulnerable in HD. Their degeneration underlies motor symptoms and striatal atrophy, the anatomical hallmark of HD...
January 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29048604/influence-of-darpp-32-genetic-variation-on-bold-activation-to-happy-faces
#20
Ninni Persson, Catarina Lavebratt, Natalie C Ebner, Håkan Fischer
Dopaminergic pathways play a crucial role in reward processing, and advanced age can modulate its efficiency. DARPP-32 controls dopaminergic function and is a chemical nexus of reward processing. In 61 younger (20-30 years) and older adults (54% ♀) (65-74 years), we examined how blood-oxygen-level dependent (BOLD) activation to emotional faces, vary over genotypes at three single nucleotide polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also assessed age-magnification of DARPP-32 effects on BOLD activation...
October 1, 2017: Social Cognitive and Affective Neuroscience
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