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https://www.readbyqxmd.com/read/29217157/functional-histamine-h3-and-adenosine-a2a-receptor-heteromers-in-recombinant-cells-and-rat-striatum
#1
Ricardo Márquez-Gómez, Meridith T Robins, Citlaly Gutiérrez-Rodelo, Juan-Manuel Arias, Jesús-Alberto Olivares-Reyes, Richard M van Rijn, José-Antonio Arias-Montaño
In the striatum, histamine H3 receptors (H3Rs) are co-expressed with adenosine A2A receptors (A2ARs) in the cortico-striatal glutamatergic afferents and the GABAergic medium-sized spiny neurons that originate from the indirect pathway of the basal ganglia. This location allows H3Rs and A2ARs to regulate the striatal GABAergic and glutamatergic transmission. However, whether these receptors can physically interact has not yet been assessed. To test this hypothesis, a heteromer-selective in vitro assay was used to detect functional complementation between a chimeric A2AR302-Gαqi4 and wild-type H3Rs in transfected HEK-293 cells...
December 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29212711/ppar%C3%AE-activation-by-bexarotene-promotes-neuroprotection-by-restoring-bioenergetic-and-quality-control-homeostasis
#2
Audrey S Dickey, Dafne N Sanchez, Martin Arreola, Kunal R Sampat, Weiwei Fan, Nicolas Arbez, Sergey Akimov, Michael J Van Kanegan, Kohta Ohnishi, Stephen K Gilmore-Hall, April L Flores, Janice M Nguyen, Nicole Lomas, Cynthia L Hsu, Donald C Lo, Christopher A Ross, Eliezer Masliah, Ronald M Evans, Albert R La Spada
Neurons must maintain protein and mitochondrial quality control for optimal function, an energetically expensive process. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that promote mitochondrial biogenesis and oxidative metabolism. We recently determined that transcriptional dysregulation of PPARδ contributes to Huntington's disease (HD), a progressive neurodegenerative disorder resulting from a CAG-polyglutamine repeat expansion in the huntingtin gene. We documented that the PPARδ agonist KD3010 is an effective therapy for HD in a mouse model...
December 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29209962/effects-of-location-and-extent-of-spine-clustering-on-synaptic-integration-in-striatal-medium-spiny-neurons-a-computational-study
#3
Mrunal Rane, Rohit Manchanda
The nucleus accumbens (NAc) is known widely for its role in the reward circuit, which is dysregulated in a number of psychological disorders. Recent evidence also suggests the contribution of this structure in spatial and gustatory memories. Because of its role in different types of memories, similar to the hippocampus, we assumed the formation of spine clusters, which are engrams of memory, to be present on dendrites of medium spiny neurons (MSNs). We found that the activation of clustered inputs resulted in sublinear summation when clusters were present on the same branch and also when inputs were distributed on different branches...
December 6, 2017: Medical & Biological Engineering & Computing
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
#4
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/29201000/striatal-g%C3%AE-olf-camp-signal-dependent-mechanism-to-generate-levodopa-induced-dyskinesia-in-parkinson-s-disease
#5
Satoshi Goto
The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA) deficiency due to a progressive degeneration of nigral dopaminergic cells. Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a long-term daily administration of levodopa often develops levodopa-induced dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the principal neurons of the striatum, which are roughly halved with striatonigral MSNs by striatopallidal MSNs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29196217/huntington-s-disease-leads-to-decrease-of-gaba-a-tonic-subunits-in-the-d2-neostriatal-pathway-and-their-relocalization-into-the-synaptic-cleft
#6
Abraham Rosas-Arellano, Carlos Tejeda-Guzmán, Enrique Lorca-Ponce, Lourdes Palma-Tirado, Carola A Mantellero, Patricio Rojas, Fanis Missirlis, Maite A Castro
GABA is a widely distributed inhibitory neurotransmitter. GABA-A receptors are hetero-pentameric channels assembled in multiple combinations from 19 available subunits; this diversity mediates phasic and tonic inhibitory synaptic potentials. Whereas GABA-A phasic receptors are located within the synaptic cleft, GABA-A tonic receptors are found peri- or extra-synaptically, where they are activated by diffusion of synaptic GABA release. In the neostriatum, GABA-A tonic subunits are present in the D2 medium-size spiny neurons...
November 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29176874/neurturin-overexpression-in-dopaminergic-neurons-induces-presynaptic-and-postsynaptic-structural-changes-in-rats-with-chronic-6-hydroxydopamine-lesion
#7
David Reyes-Corona, Nallely Vázquez-Hernández, Lourdes Escobedo, Carlos E Orozco-Barrios, Jose Ayala-Davila, Mario Gil Moreno, Miriam E Amaro-Lara, Yazmin M Flores-Martinez, Armando J Espadas-Alvarez, Manuel A Fernandez-Parrilla, Juan A Gonzalez-Barrios, M E Gutierrez-Castillo, Ignacio González-Burgos, Daniel Martinez-Fong
The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system...
2017: PloS One
https://www.readbyqxmd.com/read/29176843/hiv-1-and-cocaine-disrupt-dopamine-reuptake-and-medium-spiny-neurons-in-female-rat-striatum
#8
Mehrak Javadi-Paydar, Robert F Roscoe, Adam R Denton, Charles F Mactutus, Rosemarie M Booze
HIV-1 and addictive drugs, such as cocaine (COC), may act in combination to produce serious neurological complications. In the present experiments, striatal brain slices from HIV-1 transgenic (Tg) and F344 control female rats were studied. First, we examined dopamine (DA) reuptake in control, HIV-1, COC-treated (5µM) and HIV-1+COC-treated, striatal slices using fast scan cyclic voltammetry. COC-treated striatal slices from F344 control animals significantly increased DA reuptake time (T80), relative to untreated control slices...
2017: PloS One
https://www.readbyqxmd.com/read/29163139/exercise-induced-neuroprotection-of-the-nigrostriatal-dopamine-system-in-parkinson-s-disease
#9
REVIEW
Lijuan Hou, Wei Chen, Xiaoli Liu, Decai Qiao, Fu-Ming Zhou
Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29163013/motor-areas-show-altered-dendritic-structure-in-an-amyotrophic-lateral-sclerosis-mouse-model
#10
Matthew J Fogarty, Erica W H Mu, Nickolas A Lavidis, Peter G Noakes, Mark C Bellingham
Objective: Motor neurons (MNs) die in amyotrophic lateral sclerosis (ALS), a clinically heterogeneous neurodegenerative disease of unknown etiology. In human or rodent studies, MN loss is preceded by increased excitability. As increased neuronal excitability correlates with structural changes in dendritic arbors and spines, we have examined longitudinal changes in dendritic structure in vulnerable neuron populations in a mouse model of familial ALS. Methods: We used a modified Golgi-Cox staining method to determine the progressive changes in dendritic structure of hippocampal CA1 pyramidal neurons, striatal medium spiny neurons, and resistant (trochlear, IV) or susceptible (hypoglossal, XII; lumbar) MNs from brainstem and spinal cord of mice over-expressing the human SOD1(G93A) (SOD1) mutation, in comparison to wild-type (WT) mice, at four postnatal (P) ages of 8-15, 28-35, 65-75, and 120 days...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29136290/the-role-of-ca-2-dependent-k-channels-at-the-rat-corticostriatal-synapses-revealed-by-paired-pulse-stimulation
#11
Angel A Robles G, Ana V Vega, Carolina Gonzalez-Sandoval, Jaime Barral
Potassium channels play an important role in modulating synaptic activity both at presynaptic and postsynaptic levels. We have shown before that presynaptically located KV and KIR channels modulate the strength of corticostriatal synapses in rat brain, but the role of other types of potassium channels at these synapses remains largely unknown. Here we show that calcium-dependent potassium channels BK-type but not SK-type channels are located presynaptically in corticostriatal synapses. We stimulated cortical neurons in rat brain slices and recorded postsynaptic excitatory potentials (EPSP) in medium spiny neurons (MSN) in dorsal neostriatum...
November 14, 2017: Synapse
https://www.readbyqxmd.com/read/29130591/familial-choreoathetosis-due-to-novel-heterozygous-mutation-in-pde10a
#12
Dhanya L Narayanan, Dipti Deshpande, Aneek Das Bhowmik, Dandu R Varma, Ashwin Dalal
PDE10A encodes a dual cAMP-cGMP phosphodiesterase that is enriched in the medium spiny neurons of the corpus striatum in the brain and plays an important role in basal ganglia circuitry. Three unrelated patients with childhood onset chorea and striatal abnormalities on MRI brain with heterozygous de novo variants in PDE10A have been described previously. Two families with eight affected individuals with biallelic mutations in PDE10A have also been described previously. We report a family with multiple affected individuals with childhood onset chorea, striatal abnormalities, and a novel heterozygous mutation, c...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29125980/molecular-insights-into-cortico-striatal-miscommunications-in-huntington-s-disease
#13
REVIEW
Matthew B Veldman, X William Yang
Huntington's disease (HD), a dominantly inherited neurodegenerative disease, is defined by its genetic cause, a CAG-repeat expansion in the HTT gene, its motor and psychiatric symptomology and primary loss of striatal medium spiny neurons (MSNs). However, the molecular mechanisms from genetic lesion to disease phenotype remain largely unclear. Mouse models of HD have been created that exhibit phenotypes partially recapitulating those in the patient, and specifically, cortico-striatal disconnectivity appears to be a shared pathogenic event shared by HD mouse models and patients...
November 7, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29123477/the-effects-of-medium-spiny-neuron-morphologcial-changes-on-basal-ganglia-network-under-external-electric-field-a-computational-modeling-study
#14
Xiaohan Zhang, Shenquan Liu, Feibiao Zhan, Jing Wang, Xiaofang Jiang
The damage of dopaminergic neurons that innervate the striatum has been considered to be the proximate cause of Parkinson's disease (PD). In the dopamine-denervated state, the loss of dendritic spines and the decrease of dendritic length may prevent medium spiny neuron (MSN) from receiving too much excitatory stimuli from the cortex, thereby reducing the symptom of Parkinson's disease. However, the reduction in dendritic spine density obtained by different experiments is significantly different. We developed a biological-based network computational model to quantify the effect of dendritic spine loss and dendrites tree degeneration on basal ganglia (BG) signal regulation...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/29121220/pathway-specific-control-of-striatal-neuron-vulnerability-by-corticostriatal-cannabinoid-cb1-receptors
#15
Andrea Ruiz-Calvo, Irene B Maroto, Raquel Bajo-Grañeras, Anna Chiarlone, Ángel Gaudioso, José J Ferrero, Eva Resel, José Sánchez-Prieto, José A Rodríguez-Navarro, Giovanni Marsicano, Ismael Galve-Roperh, Luigi Bellocchio, Manuel Guzmán
The vast majority of neurons within the striatum are GABAergic medium spiny neurons (MSNs), which receive glutamatergic input from the cortex and thalamus, and form two major efferent pathways: the direct pathway, expressing dopamine D1 receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified in animal models of striatal damage, the molecular factors that dictate a selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown...
October 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29103081/a-randomized-multiple-dose-pharmacokinetic-study-of-a-novel-pde10a-inhibitor-tak-063-in-subjects-with-stable-schizophrenia-and-japanese-subjects-and-modeling-of-exposure-relationships-to-adverse-events
#16
Paul Goldsmith, John Affinito, Maggie McCue, Max Tsai, Stefan Roepcke, Jinhui Xie, Lev Gertsik, Thomas A Macek
BACKGROUND: Phosphodiesterase 10A (PDE10A) is selectively expressed in medium spiny neurons of the striatum. TAK-063 is a selective inhibitor of PDE10A in clinical development for the treatment of schizophrenia. OBJECTIVES: Safety, tolerability, and pharmacokinetics (PK) of TAK-063 were evaluated following multiple rising oral doses, and PK/adverse event (AE) models were developed to characterize the relationship between TAK-063 exposure and incidence of specific AEs...
December 2017: Drugs in R&D
https://www.readbyqxmd.com/read/29097596/ck2-oppositely-modulates-l-dopa-induced-dyskinesia-via-striatal-projection-neurons-expressing-d1-or-d2-receptors
#17
Marisol Cortés, Lauren Malave, Julia Castello, Marc Flajolet, M Angela Cenci, Eitan Friedman, Heike Rebholz
We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1- and adenosine A2a receptor signaling in the striatum. Ablation of CK2 in D1-receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2a antagonist, caffeine. Since both, D1 and A2a receptors, play major roles in the cellular responses to L-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of L-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#18
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/29068002/engineered-d2r-variants-reveal-the-balanced-and-biased-contributions-of-g-protein-and-%C3%AE-arrestin-to-dopamine-dependent-functions
#19
Samuel J Rose, Thomas F Pack, Sean M Peterson, Kaitlin Payne, Emiliana Borrelli, Marc G Caron
The dopamine D2 receptor (D2R), like many G-protein coupled-receptors, signals through G-protein and β-arrestin-dependent pathways. Preferential activation of one of these pathways is termed functional selectivity or biased signaling and is a promising therapeutic strategy. Though biased signaling through D2Rs has been demonstrated, acquiring the mechanistic details of biased D2R/G-protein and D2R/β-arrestin signaling in vivo has been challenging due to the lack of techniques that specifically target these interactions in discrete cell populations...
October 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29057906/distinct-retinoic-acid-receptor-rar-isotypes-control-differentiation-of-embryonal-carcinoma-cells-to-dopaminergic-or-striatopallidal-medium-spiny-neurons
#20
Anna Podleśny-Drabiniok, Joanna Sobska, Angel R de Lera, Krystyna Gołembiowska, Katarzyna Kamińska, Pascal Dollé, Małgorzata Cebrat, Wojciech Krężel
Embryonal carcinoma (EC) cells are pluripotent stem cells extensively used for studies of cell differentiation. Although retinoic acid (RA) is a powerful inducer of neurogenesis in EC cells, it is not clear what specific neuronal subtypes are generated and whether different RAR isotypes may contribute to such neuronal diversification. Here we show that RA treatment during EC embryoid body formation is a highly robust protocol for generation of striatal-like GABAergic neurons which display molecular characteristics of striatopallidal medium spiny neurons (MSNs), including expression of functional dopamine D2 receptor...
October 20, 2017: Scientific Reports
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