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https://www.readbyqxmd.com/read/28223211/sensitizing-exposure-to-amphetamine-increases-ampa-receptor-phosphorylation-without-increasing-cell-surface-expression-in-the-rat-nucleus-accumbens
#1
Qiang Wang, Dongdong Li, Nancy Bubula, Matthew R Campioni, Daniel S McGehee, Paul Vezina
Exposure to psychostimulants like cocaine or amphetamine leads to long-lasting sensitization of their behavioral and neurochemical effects. Here we characterized changes in AMPA receptor distribution and phosphorylation state in the rat nucleus accumbens (NAcc) weeks after amphetamine exposure to assess their potential contribution to sensitization by this drug. Using protein cross-linking, biochemical, subcellular fractionation, and slice electrophysiological approaches in the NAcc, we found that, unlike cocaine, previous exposure to amphetamine did not increase cell surface levels of either GluA1 or GluA2 AMPA receptor subunits, redistribution of these subunits to the synaptic or perisynaptic cellular membrane domains, protein-protein associations required to support the accumulation and retention of AMPA receptors in the PSD, or the peak amplitude of AMPA receptor mediated mEPSCs recorded in NAcc slices...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28194132/molecular-imaging-markers-to-track-huntington-s-disease-pathology
#2
REVIEW
Heather Wilson, Rosa De Micco, Flavia Niccolini, Marios Politis
Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28194040/abnormal-degradation-of-the-neuronal-stress-protective-transcription-factor-hsf1-in-huntington-s-disease
#3
Rocio Gomez-Pastor, Eileen T Burchfiel, Daniel W Neef, Alex M Jaeger, Elisa Cabiscol, Spencer U McKinstry, Argenia Doss, Alejandro Aballay, Donald C Lo, Sergey S Akimov, Christopher A Ross, Cagla Eroglu, Dennis J Thiele
Huntington's Disease (HD) is a neurodegenerative disease caused by poly-glutamine expansion in the Htt protein, resulting in Htt misfolding and cell death. Expression of the cellular protein folding and pro-survival machinery by heat shock transcription factor 1 (HSF1) ameliorates biochemical and neurobiological defects caused by protein misfolding. We report that HSF1 is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human HD iPSCs and in brain samples from patients with HD...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28191598/diacylglycerol-kinase-%C3%AE%C2%B5-localizes-to-subsurface-cisterns-of-cerebellar-purkinje-cells
#4
Yasukazu Hozumi, Hiroki Fujiwara, Kenya Kaneko, Satoshi Fujii, Matthew K Topham, Masahiko Watanabe, Kaoru Goto
Following activation of Gq protein-coupled receptors, phospholipase C yields a pair of second messengers: diacylglycerol (DG) and inositol 1,4,5-trisphosphate. Diacylglycerol kinase (DGK) phosphorylates DG to produce phosphatidic acid, another second messenger. Of the DGK family, DGKε is the only DGK isoform that exhibits substrate specificity for DG with an arachidonoyl acyl chain at the sn-2 position. Recently, we demonstrated that hydrophobic residues in the N-terminus of DGKε play an important role in targeting the endoplasmic reticulum in transfected cells...
February 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28167675/arpp-16-is-a-striatal-enriched-inhibitor-of-protein-phosphatase-2a-regulated-by-microtubule-associated-serine-threonine-kinase-3-mast-3-kinase
#5
Erika C Andrade, Veronica Musante, Atsuko Horiuchi, Hideo Matsuzaki, A Harrison Brody, Terence Wu, Paul Greengard, Jane R Taylor, Angus C Nairn
: ARPP-16 (cAMP-Regulated Phospho-Protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons (MSNs) of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28167674/ventrolateral-striatal-medium-spiny-neurons-positively-regulate-food-incentive-goal-directed-behavior-independently-of-d1-and-d2-selectivity
#6
Akiyo Natsubori, Iku Tsustui-Kimura, Hiroshi Nishida, Youcef Bouchekioua, Hiroshi Sekiya, Motokazu Uchigashima, Masahiko Watanabe, Alban de Kerchove d'Exaerde, Masaru Mimura, Norio Takata, Kenji F Tanaka
: The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28145402/dysfunction-of-ventrolateral-striatal-dopamine-receptor-type-2-expressing-medium-spiny-neurons-impairs-instrumental-motivation
#7
Iku Tsutsui-Kimura, Hiroyuki Takiue, Keitaro Yoshida, Ming Xu, Ryutaro Yano, Hiroyuki Ohta, Hiroshi Nishida, Youcef Bouchekioua, Hideyuki Okano, Motokazu Uchigashima, Masahiko Watanabe, Norio Takata, Michael R Drew, Hiromi Sano, Masaru Mimura, Kenji F Tanaka
Impaired motivation is present in a variety of neurological disorders, suggesting that decreased motivation is caused by broad dysfunction of the nervous system across a variety of circuits. Based on evidence that impaired motivation is a major symptom in the early stages of Huntington's disease, when dopamine receptor type 2-expressing striatal medium spiny neurons (D2-MSNs) are particularly affected, we hypothesize that degeneration of these neurons would be a key node regulating motivational status. Using a progressive, time-controllable, diphtheria toxin-mediated cell ablation/dysfunction technique, we find that loss-of-function of D2-MSNs within ventrolateral striatum (VLS) is sufficient to reduce goal-directed behaviours without impairing reward preference or spontaneous behaviour...
February 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28137879/differentiation-of-human-telencephalic-progenitor-cells-into-msns-by-inducible-expression-of-gsx2-and-ebf1
#8
Andrea Faedo, Angela Laporta, Alice Segnali, Maura Galimberti, Dario Besusso, Elisabetta Cesana, Sara Belloli, Rosa Maria Moresco, Marta Tropiano, Elisa Fucà, Stefan Wild, Andreas Bosio, Alessandro E Vercelli, Gerardo Biella, Elena Cattaneo
Medium spiny neurons (MSNs) are a key population in the basal ganglia network, and their degeneration causes a severe neurodegenerative disorder, Huntington's disease. Understanding how ventral neuroepithelial progenitors differentiate into MSNs is critical for regenerative medicine to develop specific differentiation protocols using human pluripotent stem cells. Studies performed in murine models have identified some transcriptional determinants, including GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1)...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137534/is-there-a-place-for-human-fetal-derived-stem-cells-for-cell-replacement-therapy-in-huntington-s-disease
#9
REVIEW
Sophie V Precious, Rike Zietlow, Stephen B Dunnett, Claire M Kelly, Anne E Rosser
Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials...
January 27, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28131769/suppression-of-inhibitory-g-protein-signaling-in-forebrain-pyramidal-neurons-triggers-plasticity-of-glutamatergic-neurotransmission-in-the-nucleus-accumbens-core
#10
Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Kevin Wickman
Cocaine and other drugs of abuse trigger long-lasting adaptations in excitatory and inhibitory neurotransmission in the mesocorticolimbic system, and this plasticity has been implicated in several key facets of drug addiction. For example, glutamatergic neurotransmission mediated by AMPA receptors (AMPAR) is strengthened in medium spiny neurons (MSNs) in the NAc core and shell during withdrawal following repeated in vivo cocaine administration. Repeated cocaine administration also suppresses inhibitory signaling mediated by G protein-gated inwardly rectifying K(+) (GIRK) channels in pyramidal neurons of the prelimbic cortex, an important source of glutamatergic input to the NAc core that has been implicated in cocaine-seeking and behavioral sensitization...
January 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28128287/striatal-neurons-expressing-d1-and-d2-receptors-are-morphologically-distinct-and-differently-affected-by-dopamine-denervation-in-mice
#11
D Gagnon, S Petryszyn, M G Sanchez, C Bories, J M Beaulieu, Y De Koninck, A Parent, M Parent
The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123013/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#12
Jasper A Heinsbroek, Daniela N Neuhofer, William C Griffin, Griffin S Siegel, Ana-Clara Bobadilla, Yonatan M Kupchik, Peter W Kalivas
: Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123012/accumbens-nnos-interneurons-regulate-cocaine-relapse
#13
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Constanza Garcia-Keller, Neringa M Stankeviciute, Rachel J Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore) and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine seeking result from glutamate spillover, initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28122201/in%C3%A2-vivo-measurement-of-pde10a-enzyme-occupancy-by-positron-emission-tomography-pet-following-single-oral-dose-administration-of-pf-02545920-in-healthy-male-subjects
#14
Marielle Delnomdedieu, Anton Forsberg, Adam Ogden, Patrik Fazio, Ching-Ray Yu, Per Stenkrona, Sridhar Duvvuri, William David, Nabil Al-Tawil, Ottavio V Vitolo, Nahid Amini, Sangram Nag, Christer Halldin, Andrea Varrone
Phosphodiesterase 10A (PDE10A) is an enzyme highly enriched in the striatal medium spiny neurons. It is involved in the regulation of cytoplasmic levels of cAMP and cGMP and signaling within the basal ganglia. This study with PDE10A radioligand [(18)F]MNI-659 was designed to measure the enzyme occupancy of PF-02545920 in 8 healthy male volunteers (48 ± 4 years) after a single oral dose (10 mg or 20 mg) and to evaluate safety and tolerability. Arterial blood sampling was performed to obtain a metabolite-corrected plasma input function for the quantification of [(18)F]MNI-659 binding to PDE10A...
January 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28115704/wave1-in-neurons-expressing-the-d1-dopamine-receptor-regulates-cellular-and-behavioral-actions-of-cocaine
#15
Ilaria Ceglia, Ko-Woon Lee, Michael E Cahill, Steven M Graves, David Dietz, Dalton J Surmeier, Eric J Nestler, Angus C Nairn, Paul Greengard, Yong Kim
Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) complex-mediated actin polymerization. Our previous studies have found WAVE1 to be inhibited by Cdk5-mediated phosphorylation in brain and to play a role in the regulation of dendritic spine morphology. Here we report that mice in which WAVE1 was knocked out (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but not mice where WAVE1 was knocked out in neurons expressing the D2 dopamine receptor (D2-KO), exhibited a significant decrease in place preference associated with cocaine...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28115486/phosphodiesterase-10a-opposite-changes-in-striato-pallidal-and-striato-entopeduncular-pathways-of-a-transgenic-mouse-model-of-dyt1-dystonia
#16
V D'Angelo, V Castelli, M Giorgi, S Cardarelli, I Saverioni, F Palumbo, P Bonsi, A Pisani, C Giampà, R Sorge, S Biagioni, F R Fusco, G Sancesario
: We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 and inhibited by D2 receptors, expressed in striato-entopeducuncular/substantia nigra or striato-pallidal pathways, respectively.PDE10A was studied in control mice (NT), and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT)...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28112453/food-restriction-induces-synaptic-incorporation-of-calcium-permeable-ampa-receptors-in-nucleus-accumbens
#17
Jiangyong Ouyang, Ioana Carcea, Jennifer K Schiavo, Kymry T Jones, Ariana Rabinowitsch, Rhonda Kolaric, Soledad Cabeza de Vaca, Robert C Froemke, Kenneth D Carr
Chronic food restriction potentiates behavioral and cellular responses to drugs of abuse and D-1 dopamine receptor agonists administered systemically or locally in the nucleus accumbens (NAc). However, the alterations in NAc synaptic transmission underlying these effects are incompletely understood. AMPA receptor trafficking is a major mechanism for regulating synaptic strength, and previous studies have shown that both sucrose and d-amphetamine rapidly alter the abundance of AMPA receptor subunits in the NAc postsynaptic density (PSD) in a manner that differs between food-restricted and ad libitum fed rats...
January 23, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#18
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28089852/dopamine-d1-receptor-agonist-treatment-attenuates-extinction-of-morphine-conditioned-place-preference-while-increasing-dendritic-complexity-in-the-nucleus-accumbens-core
#19
Kendra L Kobrin, Danielle T Arena, Stephen C Heinrichs, Olivia H Nguyen, Gary B Kaplan
The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions...
January 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-hesc-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#20
C P J Hunt, C W Pouton, J M Haynes
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning WNT and SHH signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
January 5, 2017: Neurochemistry International
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