Abstract
We have for the first time generated a monoclonal antibody against DARPP-32. Enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting were used to screen the hybridomas. As a result, one MAb named Y8 (IgG1) was characterized, which bound to the native DARPP-32 protein. Then the MAb was u...
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PMID: 20715994
PDF is available here.
Abstract
The composite expression score (CES), calculated from immunostaining patterns, increased significantly from normal or gastritis to metaplasia, dysplasia, and adenocarcinoma (P < .001). In patients with normal stomach or gastritis and tumor samples, a 76% and 77% chance, respectively, was found (P <...
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PMID: 20580047
PDF is available here.
Abstract
We examined the impact of treatment with Cdk5 inhibitor, roscovitine, on the severity of LID in a rat model of Parkinson's disease (PD) induced by 6-OHDA. The expressions of Cdk5 and phosphorylation of dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) in the striatum of LID rats were...
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PMID: 20504213
PDF is available here.
Abstract
We tested whether phosphodiesterase 5 (PDE5) inhibitors, sildenafil and vardenafil, would afford protection against 3-nitropropionic acid (3NP), which produces striatal lesions that closely mimic some of the neuropathological features of Huntington's Disease (HD). The neurotoxin was given over 5 day...
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PMID: 20109548
PDF is available here.
Abstract
We hypothesized that, in the VTA, dopamine type 1-like receptor (D1)-mediated increases in progesterone (P4)-facilitated lordosis involve DARPP-32. To investigate this, ovariectomized hamsters and rats, primed with estradiol (E2; 10 microg), received infusions to the VTA of saline vehicle or sense o...
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PMID: 19782104
PDF is available here.
Abstract
We investigated in the mouse, a species suited for transgenic studies, the mechanisms of locomotor sensitization showed by the increased response to a second injection of drug (two-injection protocol of sensitization, TIPS). The first cocaine injection induced a locomotor sensitization that was comp...
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PMID: 19759531
PDF is available here.
Abstract
We investigated the signal transduction cascade modulated by adenosine A(2A) receptors under chronic dopamine deficiency in the "weaver" mouse. We determined the phosphorylation state of cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at Thr34 and of Extracellular Signal-regulated Protein Kinases...
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PMID: 19852993
PDF is available here.
Abstract
Females had higher protein levels of DARPP-32, P-Thr34-DARPP-32, calcineurin A (CaN-A; catalytic subunit of PP-2B), and calcineurin B (CaN-B; regulatory subunit of PP-2B) than males 5 min after saline treatment. In females, CaN-A protein levels were also higher at 15 min and PP-1 protein levels were...
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PMID: 18985320
PDF is available here.
Abstract
Drug addiction represents a pathological form of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry. The aberrant behavioral phenotypes can be assessed by an animal model of drug-induced behavioral sen...
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PMID: 19403004
PDF is available here.
Abstract
We now show that ethanol treatment of D(1) receptor-expressing cells decreases D(1) receptor phosphorylation and concurrently potentiates dopamine-stimulated cAMP accumulation. Protein kinase C (PKC) inhibitors mimic the effects of ethanol on D(1) receptor phosphorylation and dopamine-stimulated cAM...
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PMID: 18288091
PDF is available here.
Abstract
We have designed an in vitro protocol combining substrates, media, and cytokines to push hES cells along the neural lineage, up to postmitotic neurons expressing striatal markers. The therapeutic potential of such hES-derived cells was further substantiated by their in vivo differentiation into stri...
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PMID: 18922775
PDF is available here.
Abstract
We show here that virtually all of the newly produced striatal neurons are calretinin (CR)-immunoreactive (+), but not DARPP-32(+), calbindin-D-28K(+), parvalbumin(+), somatostatin(+), or choline acetyltransferase(+). Retroviral fate-mapping studies confirm that these newly born CR(+) neurons are in...
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PMID: 18720478
PDF is available here.
Abstract
We developed transgenic mice that, within the forebrain, selectively express a pathogenic huntingtin species in the MSNs, specifically excluding the neocortex. These mice develop a number of abnormalities characteristic of pan-cellular HD mouse models, including intranuclear inclusion bodies, motor...
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PMID: 18632688
PDF is available here.
Abstract
Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability....
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PMID: 18701760
PDF is available here.
Abstract
We identified ephrin/Eph family members as guidance cues that regulate matrix/striosome compartmentalization. We found that EphA4 and its ephrin ligands displayed specific temporal patterns of expression and function that play a significant role in the spatial segregation of matrix and striosome neu...
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PMID: 18755772
PDF is available here.
Abstract
We have previously shown that beta-adducin is phosphorylated by Fyn at tyrosine489 in the rat brain and bound to its Src-homology 2 domain. In the present study, we examined the immunohistochemical localization of the tyrosine489-phosphorylated form of beta-adducin (pY489-beta-adducin) in the rat br...
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PMID: 18634768
PDF is available here.
Abstract
We constructed a computer model based on experimental data. In this work we discovered unexpected responses of DARPP-32 at fast timescales. An equally important outcome of the work was to identify areas where additional work is needed in order to understand intracellular signaling at the systems lev...
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PMID: 18756427
PDF is available here.
Felix J Bode,
Michael Stephan,
Hendrik Suhling,
Reinhard Pabst,
Rainer H Straub,
Kerstin A Raber,
Michael Bonin,
Huu Phuc Nguyen,
Olaf Riess,
Andreas Bauer,
Charlotte Sjoberg,
Asa Petersén and
Stephan von Hörsten
Abstract
We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) mor...
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PMID: 18502785
PDF is available here.
Abstract
We hypothesized that these drugs exert differential effects on striatonigral and striatopallidal neurons, which comprise distinct output pathways of the basal ganglia. To directly test this idea, we developed bacterial artificial chromosome transgenic mice that allowed the analysis of DARPP-32 phosp...
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PMID: 18622401
PDF is available here.
Abstract
We have used western blot analysis to examine changes in phosphorylation of cAMP-response element binding protein (CREB), dopamine- and cyclic AMP-regulated phosphoprotein 32 (DARPP-32), extracellular signal-regulated kinase (ERK) and GluR1, key molecular substrates altered by cocaine, in the nucleu...
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PMID: 18554320
PDF is available here.
Abstract
We wished to determine if DARPP-32 gene expression and variation at selected SNPs correlated significantly with patient phenotypes. We performed RT-PCR to quantify DARPP-32 mRNA from brain samples (Brodmann Area 46) donated by the Stanley Medical Research Institute (SMRI, Array Collection): 35 from...
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PMID: 18573638
PDF is available here.
Abstract
We have examined the effect of exposure to a drug-associated context on the expression of morphine psychomotor sensitization. We show that sensitization is markedly increased in mice examined 4 weeks after the last morphine injection. In addition, this incubation period confers to the environment pa...
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PMID: 18614186
PDF is available here.
Abstract
We reported > or =15-fold up-regulation of mRNA and protein levels of t-DARPP in HR-5 and HR-6 cells compared with their progenitor BT-474 trastuzumab-sensitive cells. The t-DARPP expression was not regulated by changes in its promoter DNA methylation levels. The SKBR-3 cells stably expressing t-DAR...
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PMID: 18579663
PDF is available here.
Abstract
We test whether DARPP-32 is required for sensitization of Drd1a responses in a PD model. In the normal dorsal striatum, there is minimal Drd1a-mediated activation of ERK1/2; however, in the PD model there is robust Drd1a-mediated activation of ERK1/2. In both wild-type and DARPP-32 knock-out mice, D...
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PMID: 18614680
PDF is available here.
Abstract
We now demonstrate that RA regulates DARPP-32 mRNA and protein in primary striatal neuronal cultures. Furthermore, DARPP-32 induction by RA in vitro requires phosphatidylinositide 3-kinase, but is independent of tropomyosin-related kinase B, cyclin-dependent kinase 5, and protein kinase B. Using pha...
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PMID: 18485106
PDF is available here.
Abstract
Organotypic cocultures of striatum, cortex, and ventral mesencephalon were used to study the anatomical and physiological development of striatal neurons in the presence or absence of cortical and nigral (SN/VTA) inputs. Striatum and cortex were dissected from prenatal (E18-E22) or early postnatal (...
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PMID: 18435420
PDF is available here.
Abstract
We observed direct synaptic connections between glutamate immunoreactive axon terminals and DARPP-32 labelled dendrites in the MSt and also in the posterolateral telencephalon (nidopallium caudolaterale, a prefrontal cortex equivalent region) and the hippocampus. Glutamate immunoreactive axons synap...
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PMID: 18498930
PDF is available here.
Alexandre Stipanovich,
Emmanuel Valjent,
Miriam Matamales,
Akinori Nishi,
Jung-Hyuck Ahn,
Matthieu Maroteaux,
Jesus Bertran-Gonzalez,
Karen Brami-Cherrier,
Hervé Enslen,
Anne-Gaëlle Corbillé,
Odile Filhol,
Angus C Nairn,
Paul Greengard,
Denis Hervé and
Jean-Antoine Girault
Abstract
We show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation...
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PMID: 18496528
PDF is available here.
Abstract
We used transgenic mice, in which enhanced green fluorescent protein (EGFP) expression was driven by D1R promoter (drd1a-EGFP) or D2R promoter (drd2-EGFP). We confirmed the expression of drd1a-EGFP in striatonigral and drd2-EGFP in striatopallidal neurons. Drd2-EGFP was also expressed in cholinergic...
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PMID: 18509028
PDF is available here.
Abstract
We did not observe a significant reduction of QA-induced pathology in assessed neuronal populations of the basal ganglia. These results indicate that sole enhancement of XIAP or Bcl-xL is not sufficient to counteract QA-induced excitotoxic insult of striatal neurons....
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PMID: 18406531
PDF is available here.
Abstract
Dopamine (DA) exerts a strong influence on inhibition in prefrontal cortex. The main cortical interneuron subtype targeted by DA are fast-spiking gamma-aminobutyric acidergic (GABAergic) cells that express the calcium-binding protein parvalbumin. D1 stimulation depolarizes these interneurons and inc...
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PMID: 17693396
PDF is available here.
Abstract
We tested the DARPP-32 gene, PPP1R1B, for association with ADHD using four polymorphic markers selected across the gene in a sample of 255 ADHD families. We did not detect evidence of association of individual marker alleles and haplotype analysis did not reveal significant association in this sampl...
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PMID: 17948899
PDF is available here.
Abstract
We systematically compare 5 HDL2 and 5 HD brains with the hypothesis that, reflecting the clinical presentation, the neuropathology of the 2 diseases would be similar. Gross and microscopic examination revealed prominent striatal neuron loss and astrocytic gliosis in a dorsal to ventral gradient in...
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PMID: 18379432
PDF is available here.
Abstract
We reasoned that increasing striatal BDNF through over-expression would slow progression of the disease if BDNF reduction plays a pivotal role in HD pathogenesis. We employed a Bdnf transgene driven by the promoter for the alpha subunit of Ca(2+)/calmodulin-dependent kinase II to over-express BDNF i...
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PMID: 18086127
PDF is available here.
Abstract
Rasagiline is a novel selective irreversible monoamine oxidase-B (MAO-B) inhibitor recently introduced for the symptomatic treatment of Parkinson disease. Like other propargylamines rasagiline has also shown neuroprotective effects independent of MAO-B-inhibition in various in vitro and in vivo mode...
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PMID: 18222424
PDF is available here.
Abstract
We did not find any changes in DARPP-32 and NCS-1 protein expression in any brain region investigated....
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PMID: 17763944
PDF is available here.
Abstract
The roles of dopamine and cyclic-AMP regulated phosphoprotein-32 (DARPP-32) in mediating dopamine (DA)-dependent modulation of corticoaccumbens transmission and intercellular coupling were examined in mouse accumbens (NAC) neurons by both intracellular sharp electrode and whole cell recordings. In w...
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PMID: 18155847
PDF is available here.
Abstract
Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadoles...
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PMID: 18234897
PDF is available here.
Abstract
We detected overexpression of t-Darpp mRNA in two thirds of gastric cancers compared with normal samples (P = 0.004). Using 20 micromol/L ceramide treatment as a model for induction of apoptosis in AGS cancer cells, we found that expression of t-Darpp led to an increase in Bcl2 protein levels and bl...
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PMID: 18199533
PDF is available here.
Liu L Hong,
Yunping Y Zhao,
Jin J Wang,
Ying Y Han,
Wei W Guo,
Haifeng H Jin,
Huihong H Zhai,
Feihu F Bai,
Xiaoyin X Zhang,
Taidong T Qiao,
Zhen Z Chen and
Daiming D Fan
Abstract
We have investigated the roles of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. The up-regulation of DARPP-32 was found to significantly enhance the sensitivity of cells of human adriamycin (ADR...
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PMID: 17492506
PDF is available here.
Abstract
Evidence that psychoactive substance use disorders, bulimia nervosa, pathological gambling, and sexual addiction share an underlying biopsychological process is summarized. Definitions are offered for addiction and addictive process, the latter being the proposed designation for the underlying biops...
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PMID: 17764663
PDF is available here.
Abstract
We will describe changes in long-term synaptic excitability following dopamine (DA) denervation and long-term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of...
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PMID: 18781674
PDF is available here.
Abstract
We determined the immunohistochemical localization of DARPP32 in the brains of a normal control group and patients with MSA. An anti-DARPP32 antibody revealed immunopositive oligodendrocytes and astrocytes widely distributed in the brains of the normal control group and the brain of patients with MS...
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PMID: 18808062
PDF is available here.
Abstract
We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted synergistically with mutated huntingtin (expHtt) to increase aggregate formation and striatal death. In the present work, we extend these observations to an in vivo system based on lentiviral-mediated expression of...
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PMID: 17905594
PDF is available here.
Abstract
We have studied the role of DARPP201032 in the regulation of voltage2010gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho2010DARPP201032, but not of the unphosphorylated form, reduced the sodium current amplitude. This effect was similar to those induc...
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PMID: 9749785
PDF is available here.
Abstract
We have examined the effect produced by systemic administration of Delta(9)-tetrahydrocannabinol (THC), the major component of marihuana and hashish, on DARPP-32. We show that THC increases DARPP-32 phosphorylation at Thr 34 both in dorsal striatum and nucleus accumbens. Time-course and dose-respons...
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PMID: 17686497
PDF is available here.
Abstract
We have developed a mathematical approach to the study of dynamical biological networks, based on combining large-scale numerical simulation with nonlinear "dimensionality reduction" methods. Our work was motivated by an interest in the complex organization of the signaling cascade centered on the n...
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PMID: 18032599
PDF is available here.
Abstract
Signaling pathways play important roles in the coordination and integration of a myriad cellular functions. Because of widespread interest in the dopaminergic pathways, the protein dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein with molecular weight of 32 kDa, known by th...
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PMID: 18020984
PDF is available here.
Abstract
We intended to investigate the significance of brain CB(1) receptors on the development of behavioral sensitization to methamphetamine. Male Sprague-Dawley rats treated with chronic methamphetamine (4 mg/kg, i.p.) for either 7 or 14 days developed behavioral sensitization to methamphetamine (1 mg/kg...
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PMID: 17953657
PDF is available here.
Abstract
We firstly investigated the roles of DARPP-32 in multidrug resistance of gastric cancer cells. Inhibition of DARPP-32 by small interfering RNA led to decreased sensitivity of cells to chemotherapeutic drugs, accompanied by increased capacity of cells to efflux adriamycin. Inhibition of DARPP-32 expr...
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PMID: 18058465
PDF is available here.
Abstract
We examined rat striatal neurons by combining immunofluorescence labeling for preprotachykinin B (PPTB), the precursor of NKB, and fluorescence in situ hybridization labeling for dopamine receptors. Fluorescent signals for D1 receptor mRNA were detected in 85-89% of PPTB-immunopositive neurons in th...
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PMID: 18028111
PDF is available here.
Abstract
Our results indicated that acute ECS produces smaller changes in the expression of DARPP-32 but, interestingly, chronic ECS increased transient expression of DARPP-32 in several time frames, in striatum and hippocampus, after the last stimulation. Results on the expression of proteins involved in si...
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PMID: 17919461
PDF is available here.
Abstract
These results suggest that the high levels of phospho-Thr75 DARPP-32 maintain PKA in a prevalent inhibited state. Furthermore, in sensitized rats the acute administration of 6-methyl-2-(phenylethynyl)-pyridine, a mGluR5 antagonist, reinstated the phosphorylation levels of Thr75- and Thr34-DARPP-32,...
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PMID: 17680995
PDF is available here.
Abstract
While cyclin-dependent kinase 5 (Cdk5) is of growing importance to neuronal signaling, its regulation remains relatively unexplored. Examination of the mechanism by which NMDA modulates the phosphorylation of protein phosphatase inhibitor-1 at Ser6 and Ser67 and dopamine- and cAMP-regulated phosphop...
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PMID: 17868322
PDF is available here.
Abstract
We investigated the phosphorylation pathways of these two proteins in response to acute cocaine administration. A single cocaine administration (30 mg/kg) increased ERK-mediated signaling proteins, phosphoryation of cAMP response element-binding protein (CREB) kinase, pp90 ribosomal S6 kinase (RSK),...
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PMID: 17920048
PDF is available here.
Abstract
We show with genetic analyses that three independent dopaminergic mechanisms contribute to reward and avoidance learning in humans. A polymorphism in the DARPP-32 gene, associated with striatal dopamine function, predicted relatively better probabilistic reward learning. Conversely, the C957T polymo...
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PMID: 17913879
PDF is available here.
Abstract
Our data demonstrated significantly increased levels of PDyn mRNA and phospho-Thr-34 DARPP-32 and significantly decreased phospho-Thr-75 DARPP-32 in LID rats compared with control and l-dopa treated groups. Following treatment of the non-competitive NMDA receptor antagonist dizocilpine (MK-801), the...
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PMID: 17884291
PDF is available here.