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https://www.readbyqxmd.com/read/28524260/presence-of-ethanol-sensitive-glycine-receptors-in-medium-spiny-neurons-in-the-mouse-nucleus-accumbens
#1
B Förstera, B Muñoz, M K Lobo, R Chandra, D M Lovinger, L G Aguayo
Alcohol abuse causes major social, economic and health-related problems worldwide. Alcohol, like other drugs of abuse, increases levels of dopamine in the nucleus accumbens, facilitating behavioural reinforcement and substance abuse. Previous studies suggested that glycine receptors (GlyRs) are involved in the regulation of accumbal dopamine levels. Here, we investigated the presence of GlyRs in accumbal dopamine receptor medium spiny neurons (MSNs) of C57BL/6J mice, analyzing mRNA expression-levels and immunoreactivity of GlyR subunits, as well as ethanol sensitivity...
May 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28503136/a-quantitative-golgi-study-of-dendritic-morphology-in-the-mice-striatal-medium-spiny-neurons
#2
Ivana Bicanic, Ana Hladnik, Zdravko Petanjek
In this study we have provided a detailed quantitative morphological analysis of medium spiny neurons (MSNs) in the mice dorsal striatum and determined the consistency of values among three groups of animals obtained in different set of experiments. Dendritic trees of 162 Golgi Cox (FD Rapid GolgiStain Kit) impregnated MSNs from 15 adult C57BL/6 mice were 3-dimensionally reconstructed using Neurolucida software, and parameters of dendritic morphology have been compared among experimental groups. The parameters of length and branching pattern did not show statistically significant difference and were highly consistent among groups...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28497110/accumbal-cholinergic-interneurons-differentially-influence-motivation-related-to-satiety-signaling
#3
Teemu Aitta-Aho, Benjamin U Phillips, Elpiniki Pappa, Y Audrey Hay, Fiona Harnischfeger, Christopher J Heath, Lisa M Saksida, Tim J Bussey, John Apergis-Schoute
Satiety, rather than all or none, can instead be viewed as a cumulative decrease in the drive to eat that develops over the course of a meal. The nucleus accumbens (NAc) is known to play a critical role in this type of value reappraisal, but the underlying circuits that influence such processes are unclear. Although NAc cholinergic interneurons (CINs) comprise only a small proportion of NAc neurons, their local impact on reward-based processes provides a candidate cell population for investigating the neural underpinnings of satiety...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28487497/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#4
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/28473645/dopamine-receptors-differentially-control-binge-alcohol-drinking-mediated-synaptic-plasticity-of-the-core-nucleus-accumbens-direct-and-indirect-pathways
#5
Xincai Ji, Sucharita Saha, Jenya Kolpakova, Melissa Guildford, Andrew R Tapper, Gilles E Martin
Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intakes, is most prevalent in young adults and a risk factor for excessive alcohol consumption and alcohol dependence. Although alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking-in-the-dark (DID) as a model of binge alcohol drinking to assess its effects on spike-timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch clamp recordings with calcium imaging and optogenetics...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28473642/selective-vulnerability-of-striatal-d2-versus-d1-dopamine-receptor-expressing-medium-spiny-neurons-in-hiv-1-tat-transgenic-male-mice
#6
Christina J Schier, William D Marks, Jason J Paris, Aaron J Barbour, Virginia D McLane, William F Maragos, A Rory McQuiston, Pamela E Knapp, Kurt F Hauser
Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology-with motor impairment a frequent manifestation of chronic infection; yet, little is known about the response of individual striatal neuron types to HIV or how this disrupts function. Consequently, we examined the morphological, electrophysiological, and anxiety-like and exploratory/locomotor behavioral effects of HIV-1 Tat in dopamine subtype 1 (D1) and dopamine subtype 2 (D2) receptor-expressing striatal medium spiny neurons (MSNs) by breeding transgenic Tat-expressing mice to Drd1a-tdTomato- or Drd2-eGFP- reporter mice...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28469074/sorcs2-mediated-nr2a-trafficking-regulates-motor-deficits-in-huntington-s-disease
#7
Qian Ma, Jianmin Yang, Teresa A Milner, Jean-Paul G Vonsattel, Mary Ellen Palko, Lino Tessarollo, Barbara L Hempstead
Motor dysfunction is a prominent and disabling feature of Huntington's disease (HD), but the molecular mechanisms that dictate its onset and progression are unknown. The N-methyl-D-aspartate receptor 2A (NR2A) subunit regulates motor skill development and synaptic plasticity in medium spiny neurons (MSNs) of the striatum, cells that are most severely impacted by HD. Here, we document reduced NR2A receptor subunits on the dendritic membranes and at the synapses of MSNs in zQ175 mice that model HD. We identify that SorCS2, a vacuolar protein sorting 10 protein-domain (VPS10P-domain) receptor, interacts with VPS35, a core component of retromer, thereby regulating surface trafficking of NR2A in MSNs...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28462942/cell-type-specific-epigenetic-editing-at-the-fosb-gene-controls-susceptibility-to-social-defeat-stress
#8
Peter J Hamilton, Dominika J Burek, Sonia I Lombroso, Rachael L Neve, Alfred J Robison, Eric J Nestler, Elizabeth A Heller
Chronic social defeat stress regulates the expression of Fosb in the nucleus accumbens (NAc) to promote the cell-type specific accumulation of ΔFosB in the two medium spiny neuron (MSN) subtypes in this region. ΔFosB is selectively induced in D1-MSNs in the NAc of resilient mice, and in D2-MSNs of susceptible mice. However, little is known about the consequences of such selective induction, particularly in D2-MSNs. This study examined how cell-type specific control of the endogenous Fosb gene in NAc regulates susceptibility to social defeat stress...
May 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28462940/chronic-nicotine-alters-corticostriatal-plasticity-in-the-striatopallidal-pathway-mediated-by-nr2b-containing-silent-synapses
#9
Jianxun Xia, Allison M Meyers, Jeff A Beeler
Smoking is the leading cause of preventable death in the U.S. and success rates for quitting remain low. High relapse rates are attributed to pervasive nicotine-reinforced associative learning of incentive cues that is highly resistant to extinction. Why such learning is so persistent is poorly understood but may arise as a consequence of neuroadaptations in synaptic plasticity induced by chronic nicotine. We used whole-cell patch clamp recording to investigate the effect of chronic nicotine (cNIC) on synaptic plasticity in dopamine D2 receptor-expressing medium spiny neurons in the indirect, striatopallidal pathway in dorsolateral striatum...
May 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28462841/design-and-optimization-of-purine-derivatives-as-in-vivo-active-pde10a-inhibitors
#10
Liu Chen, Danqi Chen, Le Tang, Jing Ren, Jiaojiao Chen, Xuechu Zhen, Yu-Chih Liu, Chenhua Zhang, Haibin Luo, Jingkang Shen, Bing Xiong
Phosphodiesterases are important enzymes regulating signal transduction mediated by second messenger molecules cAMP or cGMP. PDE10A is a unique member in the PDE family because of its selective expression in medium spiny neurons. It is recognized as anti-psychotic drug target. Based on the structural similarity between our previous chemistry work on 8-aminoimidazo[1,2-a]pyrazines and the PDE10A inhibitors reported by Bartolome-Nebreda et al., we initialized a project for developing PDE10A inhibitors. After several rounds of optimization, we were able to obtain a few compounds with good PDE10A enzymatic activity...
April 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28462043/lack-of-riluzole-efficacy-in-the-progression-of-the-neurodegenerative-phenotype-in-a-new-conditional-mouse-model-of-striatal-degeneration
#11
Grzegorz Kreiner, Katarzyna Rafa-Zabłocka, Piotr Chmielarz, Monika Bagińska, Irena Nalepa
BACKGROUND: Huntington's disease (HD) is a rare familial autosomal dominant neurodegenerative disorder characterized by progressive degeneration of medium spiny neurons (MSNs) located in the striatum. Currently available treatments of HD are only limited to alleviating symptoms; therefore, high expectations for an effective therapy are associated with potential replacement of lost neurons through stimulation of postnatal neurogenesis. One of the drugs of potential interest for the treatment of HD is riluzole, which may act as a positive modulator of adult neurogenesis, promoting replacement of damaged MSNs...
2017: PeerJ
https://www.readbyqxmd.com/read/28453524/peripheral-huntingtin-silencing-does-not-ameliorate-central-signs-of-disease-in-the-b6-httq111-mouse-model-of-huntington-s-disease
#12
Sydney R Coffey, Robert M Bragg, Shawn Minnig, Seth A Ament, Jeffrey P Cantle, Anne Glickenhaus, Daniel Shelnut, José M Carrillo, Dominic D Shuttleworth, Julie-Anne Rodier, Kimihiro Noguchi, C Frank Bennett, Nathan D Price, Holly B Kordasiewicz, Jeffrey B Carroll
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD...
2017: PloS One
https://www.readbyqxmd.com/read/28438992/microglial-nf%C3%AE%C2%BAb-tnf%C3%AE-hyperactivation-induces-obsessive-compulsive-behavior-in-mouse-models-of-progranulin-deficient-frontotemporal-dementia
#13
Grietje Krabbe, S Sakura Minami, Jon I Etchegaray, Praveen Taneja, Biljana Djukic, Dimitrios Davalos, David Le, Iris Lo, Lihong Zhan, Meredith C Reichert, Faten Sayed, Mario Merlini, Michael E Ward, David C Perry, Suzee E Lee, Ana Sias, Christopher N Parkhurst, Wen-Biao Gan, Katerina Akassoglou, Bruce L Miller, Robert V Farese, Li Gan
Frontotemporal dementia (FTD) is the second most common dementia before 65 years of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune disorders, accompanied by elevated levels of tissue necrosis factor (TNF) α. We examined behavioral alterations related to obsessive-compulsive disorder (OCD) and the role of TNFα and related signaling pathways in FTD patients with GRN mutations and in mice lacking progranulin (PGRN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433741/loss-of-the-neurodevelopmental-gene-zswim6-alters-striatal-morphology-and-motor-regulation
#14
David J Tischfield, Dave K Saraswat, Andrew Furash, Stephen C Fowler, Marc V Fuccillo, Stewart A Anderson
The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown function that has been associated with schizophrenia and limited educational attainment by three independent genome-wide association studies. Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability. Despite the growing number of studies implicating ZSWIM6 as an important regulator of brain development, its role in this process has never been examined...
April 19, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28414301/striatopallidal-dysfunction-underlies-repetitive-behavior-in-shank3-deficient-model-of-autism
#15
Wenting Wang, Chenchen Li, Qian Chen, Marie-Sophie van der Goes, James Hawrot, Annie Y Yao, Xian Gao, Congyi Lu, Ying Zang, Qiangge Zhang, Katherine Lyman, Dongqing Wang, Baolin Guo, Shengxi Wu, Charles R Gerfen, Zhanyan Fu, Guoping Feng
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414299/an-indirect-route-to-repetitive-actions
#16
David M Lovinger
It is increasingly evident that there is a genetic contribution to autism spectrum disorders (ASDs) and other neural disorders involving excessive repetition of action sequences. Among the implicated genes in these disorders are those encoding postsynaptic scaffolding proteins with roles in synaptic transmission and plasticity. Several mouse models harboring synonymous mutations have shown alterations in synaptic transmission within the striatum, which has key roles in controlling actions and action sequences...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28402856/chd8-mutation-leads-to-autistic-like-behaviors-and-impaired-striatal-circuits
#17
Randall J Platt, Yang Zhou, Ian M Slaymaker, Ashwin S Shetty, Niels R Weisbach, Jin-Ah Kim, Jitendra Sharma, Mitul Desai, Sabina Sood, Hannah R Kempton, Gerald R Crabtree, Guoping Feng, Feng Zhang
Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically defined models can provide an entry point to studying the molecular underpinnings of this disorder. We generated germline mutant mice with loss-of-function mutations in Chd8, a de novo mutation strongly associated with ASD, and demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and craniofacial abnormalities similar to patient phenotypes. Chd8(+/-) mice display a broad, brain-region-specific dysregulation of major regulatory and cellular processes, most notably histone and chromatin modification, mRNA and protein processing, Wnt signaling, and cell-cycle regulation...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28392304/morphological-dendritic-spine-changes-of-medium-spiny-neurons-in-the-nucleus-accumbens-in-6-hydroxydopamine-lesioned-rats-treated-with-levodopa
#18
Yukihisa Funamizu, Haruo Nishijima, Tatsuya Ueno, Shinya Ueno, Hiroki Mizukami, Soroku Yagihashi, Masahiko Tomiyama
The mechanisms of dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) remain unclear, although it is known that the nucleus accumbens (NAc) plays a role in its development. Based on the hypothesis that DDS and levodopa-induced dyskinesia (LID) share a pathophysiological basis, we investigated dendritic spine morphology of medium spiny neurons (MSNs) in the NAc of a rat model of LID, because spine enlargement in MSNs of the caudate/putamen has been proposed to be a morphological hallmark of LID...
April 6, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28391016/fasting-biases-%C3%AE-opioid-receptors-toward-%C3%AE-arrestin2-dependent-signaling-in-the-accumbens-shell
#19
Simona Scheggi, Alberto Ferrari, Teresa Pelliccia, Paola Devoto, Maria Graziella De Montis, Carla Gambarana
The μ-opioid receptor (MOR) and dopamine D1 receptor are co-expressed in the medium spiny neurons of striatal areas and the signaling pathways activated by these two receptors are in functional competition. However, in certain conditions an integrated response mediated by the dopamine D1 receptor transduction system is observed. In mice, morphine administration induces hypermotility and this response has been described in terms of a β-arrestin2-dependent mechanism that favors prevalent dopamine D1 receptor activation...
June 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28391013/p35-hemizygosity-activates-akt-but-does-not-improve-motor-function-in-the-yac128-mouse-model-of-huntington-s-disease
#20
Kevin H J Park, Sonia Franciosi, Kristina Parrant, Ge Lu, Blair R Leavitt
Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting from N-terminal polyglutamine expansion in the huntingtin protein. A relatively selective and early loss of medium spiny neurons in the striatum is a hallmark of HD neuropathology. Although the exact mechanism of mutant huntingtin-mediated neurodegeneration is unclear, recent evidence suggests that NMDA-receptor-mediated excitotoxicity is involved. Our previously published findings show that decreasing levels of the cdk5 activators, p35 and p25, reduces NMDA receptor-mediated excitotoxicity in striatal neurons in vivo...
June 3, 2017: Neuroscience
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