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https://www.readbyqxmd.com/read/28694434/laquinimod-treatment-in-the-r6-2-mouse-model
#1
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
#2
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
#3
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 (D2R) 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...
June 5, 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
#4
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
#5
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
#6
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
#7
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...
May 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28487497/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#8
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...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424060/effects-of-a-combination-treatment-of-kd5040-and-l-dopa-in-a-mouse-model-of-parkinson-s-disease
#9
Sora Ahn, Taek-Jin Song, Seong-Uk Park, Songhee Jeon, Jongpil Kim, Joo-Young Oh, Jaehwan Jang, Sanhwa Hong, Min-A Song, Hye-Seoung Shin, Young-Rim Jung, Hi-Joon Park
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28413862/a-simple-strategy-for-culturing-morphologically-conserved-rat-hypothalamic-tanycytes
#10
Pablo Nicolás De Francesco, Daniel Castrogiovanni, Maia Uriarte, Victoria Frassa, Francina Agosti, Jesica Raingo, Mario Perello
Hypothalamic tanycytes are specialized bipolar ependymal cells that line the floor of the third ventricle. Given their strategic location, tanycytes are believed to play several key functions including being a selective barrier and controlling the amount of hypothalamic-derived factors reaching the anterior pituitary. The in vitro culture of these cells has proved to be difficult. Here, we report an improved method for the generation of primary cultures of rat hypothalamic tanycytes. Ependymal cultures were derived from tissue dissected out of the median eminence region of 10-day-old rats and cultured in a chemically defined medium containing DMEM:F12, serum albumin, insulin, transferrin and the antibiotic gentamycin...
April 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28411274/posterior-orbitofrontal-and-anterior-cingulate-pathways-to-the-amygdala-target-inhibitory-and-excitatory-systems-with-opposite-functions
#11
Basilis Zikopoulos, Malin Höistad, Yohan John, Helen Barbas
The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28348379/genetic-evidence-for-role-of-integration-of-fast-and-slow-neurotransmission-in-schizophrenia
#12
A Devor, O A Andreassen, Y Wang, T Mäki-Marttunen, O B Smeland, C-C Fan, A J Schork, D Holland, W K Thompson, A Witoelar, C-H Chen, R S Desikan, L K McEvoy, S Djurovic, P Greengard, P Svenningsson, G T Einevoll, A M Dale
The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ...
June 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28257887/muscarinic-acetylcholine-m4-receptors-play-a-critical-role-in-oxotremorine-induced-darpp-32-phosphorylation-at-threonine-75-in-isolated-medium-spiny-neurons
#13
Liqun Liu, Yuqi Huang, Qing Huang, Zhe Zhao, Jianqiang Yu, Liyun Wang
Dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) play essential roles in dopamine (DA) transmission in the striatum. It is suggested that a link exists between muscarinic acetylcholine receptors (mAChRs) and DA/DARPP-32 signaling, but the molecular mechanisms mediating this relationship have not been elucidated. The predominant mAChRs subtypes in the striatum are M1 and M4. In this study, we investigated the functions of these two receptors, particularly M4, in regulating cAMP production and DARPP-32 phosphorylation in rat striatal medium spiny neurons (MSNs)...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#14
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
April 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28182673/the-expanded-cag-repeat-in-the-huntingtin-gene-as-target-for-therapeutic-rna-modulation-throughout-the-hd-mouse-brain
#15
Nicole A Datson, Anchel González-Barriga, Eleni Kourkouta, Rudie Weij, Jeroen van de Giessen, Susan Mulders, Outi Kontkanen, Taneli Heikkinen, Kimmo Lehtimäki, Judith C T van Deutekom
The aim of these studies was to demonstrate the therapeutic capacity of an antisense oligonucleotide with the sequence (CUG)7 targeting the expanded CAG repeat in huntingtin (HTT) mRNA in vivo in the R6/2 N-terminal fragment and Q175 knock-in Huntington's disease (HD) mouse models. In a first study, R6/2 mice received six weekly intracerebroventricular infusions with a low and high dose of (CUG)7 and were sacrificed 2 weeks later. A 15-60% reduction of both soluble and aggregated mutant HTT protein was observed in striatum, hippocampus and cortex of (CUG)7-treated mice...
2017: PloS One
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
#16
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 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. We find that ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A, and that phosphorylation of ARPP-16 at Ser46 by MAST3 kinase converts the protein into a selective inhibitor of B55α- and B56δ-containing heterotrimeric forms of PP2A...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-human-embryonic-stem-cell-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#17
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 hedgehog (SHH) signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
June 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28052701/potential-for-targeting-dopamine-darpp-32-signaling-in-neuropsychiatric-and-neurodegenerative-disorders
#18
REVIEW
Akinori Nishi, Takahide Shuto
Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease...
March 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27998980/glutamate-counteracts-dopamine-pka-signaling-via-dephosphorylation-of-darpp-32-ser-97-and-alteration-of-its-cytonuclear-distribution
#19
Akinori Nishi, Miriam Matamales, Veronica Musante, Emmanuel Valjent, Mahomi Kuroiwa, Yosuke Kitahara, Heike Rebholz, Paul Greengard, Jean-Antoine Girault, Angus C Nairn
The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27994542/the-retrograde-connections-and-anatomical-segregation-of-the-g%C3%A3-ttingen-minipig-nucleus-accumbens
#20
Anders C Meidahl, Dariusz Orlowski, Jens C H Sørensen, Carsten R Bjarkam
Nucleus accumbens (NAcc) has been implicated in several psychiatric disorders such as treatment resistant depression (TRD), and obsessive-compulsive disorder (OCD), and has been an ongoing experimental target for deep brain stimulation (DBS) in both rats and humans. In order to translate basic scientific results from rodents to the human setting a large animal model is needed to thoroughly study the effect of such therapeutic interventions. The aim of the study was, accordingly, to describe the basic anatomy of the Göttingen minipig NAcc and its retrograde connections...
2016: Frontiers in Neuroanatomy
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