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DARPP-32

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https://www.readbyqxmd.com/read/29107639/cjun-n-terminal-kinase-jnk-mediates-cortico-striatal-signaling-in-a-model-of-parkinson-s-disease
#1
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)...
October 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29100151/aripiprazole-relieves-motivational-anhedonia-in-rats
#2
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...
October 20, 2017: 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
#3
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
#4
Matthew F Lazenka, Minho Kang, Dipanjana Datta De, Dana E Selley, Laura J Sim-Selley
Introduction: Repeated administration of abused drugs, including Δ(9)-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
#5
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...
October 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29048604/influence-of-darpp-32-genetic-variation-on-bold-activation-to-happy-faces
#6
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
https://www.readbyqxmd.com/read/29024103/functional-interleukin-6-receptor-%C3%AE-is-located-to-tanycytes-at-the-base-of-the-third-ventricle
#7
Fredrik Anesten, Cristiano Santos, Edwin Gidestrand, Erik Schéle, Vilborg Pálsdóttir, Teodor Swedung-Wettervik, Björn Meister, Karolina Patrycja Skibicka, John-Olov Jansson
Interleukin-6 (IL-6) (-) /(-) mice develop mature onset obesity, while intracerebroventricular (ICV) injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in cerebrospinal fluid (CSF) have been reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the 3(rd) ventricle in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL-6 in the CSF. With immunohistochemistry using a well characterized antibody directed against the ligand binding receptor for IL-6, IL-6 receptor α (IL-6Rα), it was found that tanycytes, identified by the two markers vimentin and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), contained IL-6Rα...
October 10, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28927719/sex-dependent-behavioral-impairments-in-the-hdhq350-mouse-line
#8
Jessica K Cao, Peter J Detloff, Richard G Gardner, Nephi Stella
Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease characterized by gradual deterioration of motor and cognitive functions and development of psychiatric deficits. Animal models provide powerful means to study the pathological processes, molecular dysfunctions and symptoms associated with HD. We performed a longitudinal behavioral study of the newly developed HdhQ350/+ mouse line, a knock-in model that expresses a repeat of 350 glutamines. We found remarkable sex-dependent differences on symptom onset and severity...
January 30, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28904862/t-darpp-is-an-elongated-monomer-that-binds-calcium-and-is-phosphorylated-by-cyclin-dependent-kinases-1-and-5
#9
Jamil Momand, Patrycja Magdziarz, You Feng, Dianlu Jiang, Elizabeth Parga, Arianna Celis, Erin Denny, Xiaoying Wang, Martin L Phillips, Estuardo Monterroso, Susan E Kane, Feimeng Zhou
t-Darpp (truncated isoform of dopamine- and cAMP-regulated phosphoprotein) is a protein encoded by the PPP1R1B gene and is expressed in breast, colon, esophageal, gastric, and prostate cancers, as well as in normal adult brain striatal cells. Overexpression of t-Darpp in cultured cells leads to increased protein kinase A activity and increased phosphorylation of AKT (protein kinase B). In HER2+ breast cancer cells, t-Darpp confers resistance to the chemotherapeutic agent trastuzumab. To shed light on t-Darpp function, we studied its secondary structure, oligomerization status, metal-binding properties, and phosphorylation by cyclin-dependent kinases 1 and 5...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28881851/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#10
REVIEW
Haitao Wang, Mohd Farhan, Jiangping Xu, Philip Lazarovici, Wenhua Zheng
Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28867659/t-darpp-stimulates-protein-kinase-a-activity-by-forming-a-complex-with-its-ri-regulatory-subunit
#11
Dirk Theile, Shuhui Geng, Erin C Denny, Jamil Momand, Susan E Kane
t-Darpp is the truncated form of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (Darpp-32) and has been demonstrated to confer resistance to trastuzumab, a Her2-targeted anticancer agent, via sustained signaling through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway and activation of protein kinase A (PKA). The mechanism of t-Darpp-mediated PKA activation is poorly understood. In the PKA holoenzyme, when the catalytic subunits are bound to regulatory subunits RI or RII, kinase activity is inhibited...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28782235/detection-of-phasic-dopamine-by-d1-and-d2-striatal-medium-spiny-neurons
#12
Cedric Yapo, Anu G Nair, Lorna Clement, Liliana R Castro, Jeanette Hellgren Kotaleski, Pierre Vincent
The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of dopamine effect on intracellular signalling remains poorly understood. We used genetically-encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation level, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively...
August 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28771234/aav5-mihtt-gene-therapy-demonstrates-suppression-of-mutant-huntingtin-aggregation-and-neuronal-dysfunction-in-a-rat-model-of-huntington-s-disease
#13
J Miniarikova, V Zimmer, R Martier, C C Brouwers, C Pythoud, K Richetin, M Rey, J Lubelski, M M Evers, S J van Deventer, H Petry, N Déglon, P Konstantinova
Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro...
October 2017: Gene Therapy
https://www.readbyqxmd.com/read/28694434/laquinimod-treatment-in-the-r6-2-mouse-model
#14
Gisa Ellrichmann, Alina Blusch, Oluwaseun Fatoba, Janine Brunner, Liat Hayardeny, Michael Hayden, Dominik Sehr, Konstanze F Winklhofer, Carsten Saft, Ralf Gold
The transgenic mouse model R6/2 exhibits Huntington's disease (HD)-like deficits and basic pathophysiological similarities. We also used the pheochromocytoma-12 (PC12)-cell-line-model to investigate the effect of laquinimod on metabolic activity. Laquinimod is an orally administered immunomodulatory substance currently under development for the treatment of multiple sclerosis (MS) and HD. As an essential effect, increased levels of BDNF were observed. Therefore, we investigated the therapeutic efficacy of laquinimod in the R6/2 model, focusing on its neuroprotective capacity...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638318/maturation-behavioral-activation-and-connectivity-of-adult-born-medium-spiny-neurons-in-a-striatal-song-nucleus
#15
Jennifer Kosubek-Langer, Lydia Schulze, Constance Scharff
Neurogenesis continues in the adult songbird brain. Many telencephalic song control regions incorporate new neurons into their existing circuits in adulthood. One song nucleus that receives many new neurons is Area X. Because this striatal region is crucial for song learning and song maintenance the recruitment of new neurons into Area X could influence these processes. As an entry point into addressing this possibility, we investigated the maturation and connectivity within the song circuit and behavioral activation of newly generated Area X neurons...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28580946/dopamine-d2-receptor-signaling-in-the-nucleus-accumbens-comprises-a-metabolic-cognitive-brain-interface-regulating-metabolic-components-of-glucose-reinforcement
#16
Michael Michaelides, Michael L Miller, Jennifer A DiNieri, Juan L Gomez, Elizabeth Schwartz, Gabor Egervari, Gene Jack Wang, Charles V Mobbs, Nora D Volkow, Yasmin L Hurd
Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders. Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously described. Here we show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-like responding for sucrose, a disaccharide consisting of fructose and glucose...
November 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28579948/modulation-of-low-voltage-activated-inward-current-permeable-to-sodium-and-calcium-by-darpp-32-drives-spontaneous-firing-of-insect-octopaminergic-neurosecretory-cells
#17
Bruno Lapied, Antoine Defaix, Maria Stankiewicz, Eléonore Moreau, Valérie Raymond
Identification of the different intracellular pathways that control phosphorylation/dephosphorylation process of ionic channels represents an exciting alternative approach for studying the ionic mechanisms underlying neuronal pacemaker activity. In the central nervous system of the cockroach Periplaneta americana, octopaminergic neurons, called dorsal unpaired median (DUM; DUM neurons), generate spontaneous repetitive action potentials. Short-term cultured adult DUM neurons isolated from the terminal abdominal ganglion (TAG) of the nerve cord were used to study the regulation of a tetrodotoxin-sensitive low-voltage-activated (LVA) channel permeable to sodium and calcium (Na/Ca), under whole cell voltage- and current-clamp conditions...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28553197/effects-of-darpp-32-genetic-variation-on-prefrontal-cortex-volume-and-episodic-memory-performance
#18
Ninni Persson, Jonas Persson, Catharina Lavebratt, Håkan Fischer
Despite evidence of a fundamental role of DARPP-32 in integrating dopamine and glutamate signaling, studies examining gene coding for DARPP-32 in relation to neural and behavioral correlates in humans are scarce. Post mortem findings suggest genotype specific expressions of DARPP-32 in the dorsal frontal lobes. Therefore, we investigated the effects of genomic variation in DARPP-32 coding on frontal lobe volumes and episodic memory. Volumetric data from the dorsolateral (DLPFC), and visual cortices (VC) were obtained from 61 younger and older adults (♀54%)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28536511/aripiprazole-facilitates-extinction-of-conditioned-fear-in-adolescent-rats
#19
Despina E Ganella, Liubov Lee-Kardashyan, Sophia J Luikinga, Danny L D Nguyen, Heather B Madsen, Isabel C Zbukvic, Russell Coulthard, Andrew J Lawrence, Jee Hyun Kim
Anxiety disorders are the most common type of mental disorder during adolescence, which is at least partly due to the resistance to extinction exhibited at this age. The dopaminergic system is known to be dysregulated during adolescence; therefore, we aimed to facilitate extinction in adolescent rats using the dopamine receptor 2 partial agonist aripiprazole (Abilify™), and examine the behavioral and neural outcomes. Adolescent rats were conditioned to fear a tone. The next day, rats received extinction 30 min after a systemic injection of either 5 mg/kg aripiprazole or vehicle, and then were tested the following day...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28495607/prenatal-exposure-to-lambda-cyhalothrin-alters-brain-dopaminergic-signaling-in-developing-rats
#20
Yogesh K Dhuriya, Pranay Srivastava, Rajendra K Shukla, Richa Gupta, Dhirendra Singh, Devendra Parmar, Aditya B Pant, Vinay K Khanna
The present study is focused to decipher the molecular mechanisms associated with dopaminergic alterations in corpus striatum of developing rats exposed prenatally to lambda-cyhalothrin (LCT), a new generation type II synthetic pyrethroid. There was no significant change in the mRNA and protein expression of DA-D1 receptors at any of the doses of LCT (0.5, 1 and 3mg/kg body weight) in corpus striatum of developing rats exposed prenatally to LCT on PD22 and PD45. Prenatal exposure to LCT (1 and 3mg/kg body weight) resulted to decrease the levels of mRNA and protein of DA-D2 receptors in corpus stratum of developing rats on PD22 as compared to controls...
July 1, 2017: Toxicology
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