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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
#1
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
#2
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
#3
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
#4
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...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28414299/an-indirect-route-to-repetitive-actions
#5
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...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28402856/chd8-mutation-leads-to-autistic-like-behaviors-and-impaired-striatal-circuits
#6
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
#7
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
#8
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...
April 6, 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
#9
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...
April 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28384268/interplay-between-periodic-stimulation-and-gabaergic-inhibition-in-striatal-network-oscillations
#10
Jovana J Belić, Arvind Kumar, Jeanette Hellgren Kotaleski
Network oscillations are ubiquitous across many brain regions. In the basal ganglia, oscillations are also present at many levels and a wide range of characteristic frequencies have been reported to occur during both health and disease. The striatum, the main input nucleus of the basal ganglia, receives massive glutamatergic inputs from the cortex and is highly susceptible to external oscillations. However, there is limited knowledge about the exact nature of this routing process and therefore, it is of key importance to understand how time-dependent, external stimuli propagate through the striatal circuitry...
2017: PloS One
https://www.readbyqxmd.com/read/28359739/2-4-dnp-improves-motor-function-preserves-medium-spiny-neuronal-identity-and-reduces-oxidative-stress-in-a-mouse-model-of-huntington-s-disease
#11
Bin Wu, Mali Jiang, Qi Peng, Gang Li, Zhipeng Hou, Ginger L Milne, Susumu Mori, Robert Alonso, John G Geisler, Wenzhen Duan
Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the gene huntingtin. There is no treatment to prevent or delay the disease course of HD currently. Oxidative stress and mitochondrial dysfunction have emerged as key determinants of the disease progression in HD. Therefore, counteracting mutant huntingtin (mHtt)-induced oxidative stress and mitochondrial dysfunction appears as a new approach to treat this devastating disease. Interestingly, mild mitochondrial uncoupling improves neuronal resistance to stress and facilitates neuronal survival...
March 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28336323/m1-muscarinic-activation-induces-long-lasting-increase-in-intrinsic-excitability-of-striatal-projection-neurons
#12
Xiaohui Lv, Jonathan W Dickerson, Jerri M Rook, Craig W Lindsley, P Jeffrey Conn, Zixiu Xiang
The dorsolateral striatum is critically involved in movement control and motor learning. Striatal function is regulated by a variety of neuromodulators including acetylcholine. Previous studies have shown that cholinergic activation excites striatal principal projection neurons, medium spiny neurons (MSNs), and this action is mediated by muscarinic acetylcholine subtype 1 receptors (M1) through modulating multiple potassium channels. In the present study, we used electrophysiology techniques in conjunction with optogenetic and pharmacological tools to determine the long-term effects of striatal cholinergic activation on MSN intrinsic excitability...
March 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28334608/parvalbumin-interneurons-modulate-striatal-output-and-enhance-performance-during-associative-learning
#13
Kwang Lee, Sandra M Holley, Justin L Shobe, Natalie C Chong, Carlos Cepeda, Michael S Levine, Sotiris C Masmanidis
The prevailing view is that striatal parvalbumin (PV)-positive interneurons primarily function to downregulate medium spiny projection neuron (MSN) activity via monosynaptic inhibitory signaling. Here, by combining in vivo neural recordings and optogenetics, we unexpectedly find that both suppressing and over-activating PV cells attenuates spontaneous MSN activity. To account for this, we find that, in addition to monosynaptic coupling, PV-MSN interactions are mediated by a competing disynaptic inhibitory circuit involving a variety of neuropeptide Y-expressing interneurons...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28323008/sub-chronic-variable-stress-induces-sex-specific-effects-on-glutamatergic-synapses-in-the-nucleus-accumbens
#14
Anna Brancato, Dana Bregman, H Francisica Ahn, Madeline L Pfau, Caroline Menard, Carla Cannizzaro, Scott J Russo, Georgia E Hodes
Men and women manifest different symptoms of depression and under current diagnostic criteria, depression is twice as prevalent in woman. However, little is known of the mechanisms contributing to these important sex differences. Sub-chronic variable stress (SCVS), a rodent model of depression, induces depression-like behaviors in female mice only, modeling clinical evidence of higher susceptibility to mood disorders in women. Accumulating evidence indicates that altered neuroplasticity of excitatory synapses in the nucleus accumbens (NAc) is a key pathophysiological feature of susceptibility to social stress in males...
March 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28317546/d1-and-d2-type-medium-spiny-neuron-contributions-to-depression
#15
Catherine Jensen Peña
No abstract text is available yet for this article.
April 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28289129/helios-expression-coordinates-the-development-of-a-subset-of-striatopallidal-medium-spiny-neurons
#16
Raquel Martín-Ibáñez, Mónica Pardo, Albert Giralt, Andrés Miguez, Inés Guardia, Lucile Marion-Poll, Cristina Herranz, Miriam Esgleas, Gerardo Garcia-Díaz Barriga, Michael J Edel, Carlos Vicario-Abejón, Jordi Alberch, Jean-Antoine Girault, Susan Chan, Philippe Kastner, Josep M Canals
Here we unravel the mechanism of action of Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons that express dopamine 2 receptor (D2R) and enkephalin (ENK). To exert this effect He is expressed in neural progenitor cells (NPCs) retaining them into the G1/G0 phase of the cell cycle. Thus, the lack of He produces an increase of S-phase entry and S-phase length of NPCs which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ) that end up dying at postnatal stages...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28272512/genetically-directed-sparse-neuronal-labeling-in-bac-transgenic-mice-through-mononucleotide-repeat-frameshift
#17
Xiao-Hong Lu, X William Yang
Mosaicism with Repeat Frameshift (MORF) allows a single Bacterial Artificial Chromosome (BAC) transgene to direct sparse labeling of genetically-defined neuronal populations in mice. The BAC transgene drives cell-type-specific transcription of an out-of-frame mononucleotide repeat that is placed between a translational start codon and a membrane-bound fluorescent protein lacking its start codon. The stochastic frameshift of the unstable repeat DNA in a subset of BAC-expressing neurons results in the in-frame translation of the reporter protein hence the sparse neuronal labeling...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28267149/striatal-phosphodiesterase-10a-and-medial-prefrontal-cortical-thickness-in-patients-with-schizophrenia-a-pet-and-mri-study
#18
R Bodén, J Persson, A Wall, M Lubberink, L Ekselius, E-M Larsson, G Antoni
The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls...
March 7, 2017: Translational 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
#19
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/28256089/striatal-activation-by-optogenetics-induces-dyskinesias-in-the-6-hydroxydopamine-rat-model-of-parkinson-disease
#20
Ledia F Hernández, Ivan Castela, Irene Ruiz-DeDiego, Jose A Obeso, Rosario Moratalla
BACKGROUND: Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. METHODS: We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle...
April 2017: Movement Disorders: Official Journal of the Movement Disorder Society
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