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https://www.readbyqxmd.com/read/29753726/two-single-nucleotide-polymorphisms-of-the-reln-gene-and-symptom-based-and-developmental-deficits-among-children-and-adolescents-with-autistic-spectrum-disorders-in-the-tianjin-china
#1
Geng-Fu Wang, Sheng Ye, Lei Gao, Yu Han, Xuan Guo, Xiao-Peng Dong, Yuan-Yuan Su, Xin Zhang
Increasing evidence has revealed that genetic variants in Reelin (RELN) gene, especially single-nucleotide polymorphisms (SNPs), correlate with autistic spectrum disorders (ASD) risk; however, no consensus have been reached. This study aimed to provide additional evidence for the association between two SNPs of RELN (i.e., rs736707, rs2229864) and ASD risk, as well as the relationship between RELN gene and symptom-based and developmental deficits of ASD patients in Chinese Han children and adolescents. 157 ASD subjects and 256 typical development (TD) controls were genotyped by TaqMan® genotyping assay...
May 10, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29724792/bigscale-an-analytical-framework-for-big-scale-single-cell-data
#2
Giovanni Iacono, Elisabetta Mereu, Amy Guillaumet-Adkins, Roser Corominas, Ivon Cuscó, Gustavo Rodríguez-Esteban, Marta Gut, Luis Alberto Pérez-Jurado, Ivo Gut, Holger Heyn
Single-cell RNA sequencing (scRNA-seq) has significantly deepened our insights into complex tissues, with the latest techniques capable of processing tens of thousands of cells simultaneously. Analyzing increasing numbers of cells, however, generates extremely large data sets, extending processing time and challenging computing resources. Current scRNA-seq analysis tools are not designed to interrogate large data sets and often lack sensitivity to identify marker genes. With bigSCale, we provide a scalable analytical framework to analyze millions of cells, which addresses the challenges associated with large data sets...
May 3, 2018: Genome Research
https://www.readbyqxmd.com/read/29680575/the-impact-of-body-mass-index-in-gene-expression-of-reelin-pathway-mediators-in-individuals-with-schizophrenia-and-mood-disorders-a-post-mortem-study
#3
Elisa Brietzke, Alisson P Trevizol, Gabriel R Fries, Mehala Subramaniapillai, Flavio Kapczinski, Roger S McIntyre, Rodrigo B Mansur
The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The "Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders" study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus)...
April 13, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29680514/brain-blood-cerebrospinal-fluid-and-serum-biomarkers-in-schizophrenia
#4
REVIEW
Alireza Mohammadi, Ehsan Rashidi, Vahid Ghasem Amooeian
Over the last decade, finding a reliable biomarker for the early detection of schizophrenia (Scz) has been a topic of interest. The main goal of the current review is to provide a comprehensive view of the brain, blood, cerebrospinal fluid (CSF), and serum biomarkers of Scz disease. Imaging studies have demonstrated that the volumes of the corpus callosum, thalamus, hippocampal formation, subiculum, parahippocampal gyrus, superior temporal gyrus, prefrontal and orbitofrontal cortices, and amygdala-hippocampal complex were reduced in patients diagnosed with Scz...
April 13, 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29590626/dcc-mediated-dab1-phosphorylation-participates-in-the-multipolar-to-bipolar-transition-of-migrating-neurons
#5
Jian-Hua Zhang, Yi-Fei Zhao, Xiao-Xiao He, Yang Zhao, Zi-Xuan He, Lei Zhang, Ying Huang, Yu-Bing Wang, Ling Hu, Lin Liu, Hua-Li Yu, Jia-Hui Xu, Ming-Ming Lai, Dong-Dong Zhao, Lei Cui, Wei-Xiang Guo, Wen-Cheng Xiong, Yu-Qiang Ding, Xiao-Juan Zhu
Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29581187/rbm4-modulates-radial-migration-via-alternative-splicing-of-dab1-during-cortex-development
#6
Dhananjaya D, Kuan-Yang Hung, Woan-Yuh Tarn
The RNA-binding motif 4 (RBM4) protein participates in cell differentiation via its role in regulating the expression of or tissue-specific or developmentally regulated mRNA splice isoforms. RBM4 is expressed in embryonic brain during development; it is initially enriched in the ventricular zone/subventricular zone and subsequently distributed throughout the cortical cortex. Rbm4a knockout brain exhibited delayed migration of late-born neurons. Using in utero electroporation, we confirmed that knockdown of RBM4 impaired cortical neuronal migration...
March 26, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29557780/neurogliaform-cortical-interneurons-derive-from-cells-in-the-preoptic-area
#7
Mathieu Niquille, Greta Limoni, Foivos Markopoulos, Christelle Cadilhac, Julien Prados, Anthony Holtmaat, Alexandre Dayer
Delineating the basic cellular components of cortical inhibitory circuits remains a fundamental issue in order to understand their specific contributions to microcircuit function. It is still unclear how current classifications of cortical interneuron subtypes relate to biological processes such as their developmental specification. Here we identified the developmental trajectory of neurogliaform cells (NGCs), the main effectors of a powerful inhibitory motif recruited by long-range connections. Using in vivo genetic lineage-tracing in mice, we report that NGCs originate from a specific pool of 5-HT3A R-expressing Hmx3+ cells located in the preoptic area (POA)...
March 20, 2018: ELife
https://www.readbyqxmd.com/read/29536172/developmental-abnormality-contributes-to-cortex-dependent-motor-impairments-and-higher-intracortical-current-requirement-in-the-reeler-homozygous-mutants
#8
Mariko Nishibe, Yu Katsuyama, Toshihide Yamashita
The motor deficit of the reeler mutants has largely been considered cerebellum related, and the developmental consequences of the cortex on reeler motor behavior have not been examined. We herein showed that there is a behavioral consequence to reeler mutation in models examined at cortex-dependent bimanual tasks that require forepaw dexterity. Using intracortical microstimulation, we found the forelimb representation in the motor cortex was significantly reduced in the reeler. The reeler cortex required a significantly higher current to evoke skeletal muscle movements, suggesting the cortical trans-synaptic propagation is disrupted...
March 13, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29535613/trpc1-channels-are-expressed-in-pyramidal-neurons-and-in-a-subset-of-somatostatin-interneurons-in-the-rat-neocortex
#9
Juan R Martinez-Galan, Ana Verdejo, Elena Caminos
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29515447/peripheral-etanercept-administration-normalizes-behavior-hippocampal-neurogenesis-and-hippocampal-reelin-and-gaba-a-receptor-expression-in-a-preclinical-model-of-depression
#10
Kyle J Brymer, Erin Y Fenton, Lisa E Kalynchuk, Hector J Caruncho
Depression is a serious psychiatric disorder frequently comorbid with autoimmune disorders. Previous work in our lab has demonstrated that repeated corticosterone (CORT) injections in rats reliably increase depressive-like behavior, impair hippocampal-dependent memory, reduce the number and complexity of adult-generated neurons in the dentate gyrus, decrease hippocampal reelin expression, and alter markers of GABAergic function. We hypothesized that peripheral injections of the TNF-α inhibitor etanercept could exert antidepressant effects through a restoration of many of these neurobiological changes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29512697/ephrin%C3%A2-b3-modulates-hippocampal-neurogenesis-and-the-reelin-signaling-pathway-in-a-pilocarpine%C3%A2-induced-model-of-epilepsy
#11
Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng
Ephrin‑B3 is important in the regulation of cell proliferation, differentiation and migration via cell‑cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin‑B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin‑B3 in pilocarpine‑induced status epilepticus (SE) rats was investigated. SYBR Green‑based reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin‑B3 and reelin pathway proteins...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29504096/peculiarities-of-cyto-and-chemoarchitectonics-of-human-entorhinal-cortex-during-the-fetal-period
#12
P A Zykin, I A Moiseenko, L A Tkachenko, R A Nasyrov, E A Tsvetkov, E I Krasnoshchekova
We studied peculiarities of the structure of human entorhinal cortex at weeks 20-26 of gestation (10 hemispheres). The samples were Nissl-stained and immunohistochemically treated with antibodies to parvalbumin, calretinin, calbindin, and cytoskeleton proteins (MAP2 and N200). 3D-reconstruction of the entorhinal cortex from serial sections was performed, caudomedial and rostrolateral areas were isolated. Parvalbumin+ cells in layer I, discrete distribution of layer II cells with colocalization of MAP2 and calretinin at the border with layer I, and two sublayers Va and Vb with MAP2+ neurons were typical for the caudomedial area...
March 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29470947/small-and-large-intestine-express-a-truncated-dab1-isoform-that-assembles-in-cell-cell-junctions-and-co-localizes-with-proteins-involved-in-endocytosis
#13
María D Vázquez-Carretero, Pablo García-Miranda, María S Balda, Karl Matter, María J Peral, Anunciación A Ilundain
Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198 , Y200 and Y220 ) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals...
February 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29442527/decreased-generation-of-c-terminal-fragments-of-apoer2-and-increased-reelin-expression-in-alzheimer-s-disease
#14
Trinidad Mata-Balaguer, Inmaculada Cuchillo-Ibañez, Miguel Calero, Isidro Ferrer, Javier Sáez-Valero
Increasing evidence indicates that altered reelin signaling could contribute to synaptic dysfunction in Alzheimer's disease (AD). We found that reelin protein and mRNA levels were increased in the AD brain (particularly at advanced Braak stages in apolipoprotein E4 noncarriers), compared with that of control subjects. The β-amyloid protein (Aβ) impairs reelin activity and increases reelin expression through a mechanism that is not yet understood. To explore that mechanism, we examined the effect of Aβ42 on DNA methylation of the RELN promoter and the processing of reelin receptor apolipoprotein E receptor 2 (ApoER2) in differentiated SH-SY5Y cells because ApoER2 C-terminal fragments (CTFs), generated after reelin binding, regulate reelin expression...
February 9, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29429939/an-attractive-reelin-gradient-establishes-synaptic-lamination-in-the-vertebrate-visual-system
#15
Vincenzo Di Donato, Flavia De Santis, Shahad Albadri, Thomas Oliver Auer, Karine Duroure, Marine Charpentier, Jean-Paul Concordet, Christoph Gebhardt, Filippo Del Bene
A conserved organizational and functional principle of neural networks is the segregation of axon-dendritic synaptic connections into laminae. Here we report that targeting of synaptic laminae by retinal ganglion cell (RGC) arbors in the vertebrate visual system is regulated by a signaling system relying on target-derived Reelin and VLDLR/Dab1a on the projecting neurons. Furthermore, we find that Reelin is distributed as a gradient on the target tissue and stabilized by heparan sulfate proteoglycans (HSPGs) in the extracellular matrix (ECM)...
March 7, 2018: Neuron
https://www.readbyqxmd.com/read/29420689/pdk1-deficit-impairs-the-development-of-the-dentate-gyrus-in-mice
#16
Min Xu, Xiaoning Han, Rui Liu, Yanjun Li, Cui Qi, Zhongzhou Yang, Chunjie Zhao, Jun Gao
3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossing Pdk1fl/fl mice with the Emx1-cre line, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3β signaling...
February 6, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29361558/rbx2-maintains-final-retinal-cell-position-in-a-dab1-dependent-and-independent-fashion
#17
Corinne L Fairchild, Keiko Hino, Jisoo S Han, Adam M Miltner, Gabriel Peinado Allina, Caileigh E Brown, Marie E Burns, Anna La Torre, Sergi Simó
The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition...
February 2, 2018: Development
https://www.readbyqxmd.com/read/29305086/the-candidate-schizophrenia-risk-gene-dgcr2-regulates-early-steps-of-corticogenesis
#18
Aude Molinard-Chenu, Alexandre Dayer
BACKGROUND: Alterations in early steps of cortical circuit assembly are thought to play a critical role in vulnerability to schizophrenia (SZ), but the pathogenic impact of SZ-risk mutations on corticogenesis remains to be determined. DiGeorge syndrome critical region 2 (DGCR2) is located in the 22q11.2 locus, whose deletion is a major risk factor for SZ. Moreover, exome sequencing of individuals with idiopathic SZ identified a rare missense mutation in DGCR2, further suggesting that DGCR2 is involved in SZ...
April 15, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29222813/reln-signaling-modulates-glioblastoma-growth-and-substrate-dependent-migration
#19
Markus Schulze, Christ Violonchi, Stefan Swoboda, Tobias Welz, Eugen Kerkhoff, Sabine Hoja, Susanne Brüggemann, Johann Simbürger, Jörg Reinders, Markus J Riemenschneider
Glioblastoma (GBM) represents the most common and most malignant type of primary brain tumor and significantly contributes to cancer morbidity and mortality. Invasion into the healthy brain parenchyma is a major feature of glioblastoma aggressiveness. Reelin (RELN) is a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning in the developing brain and sustains functionality in the adult brain. We here show that both RELN and its main downstream effector DAB1 are silenced in glioblastoma as compared to non-neoplastic tissue and mRNA expression is inversely correlated with malignancy grade...
December 8, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29138282/trajectory-analysis-unveils-reelin-s-role-in-the-directed-migration-of-granule-cells-in-the-dentate-gyrus
#20
Shaobo Wang, Bianka Brunne, Shanting Zhao, Xuejun Chai, Jiawei Li, Jeremie Lau, Antonio Virgilio Failla, Bernd Zobiak, Mirjam Sibbe, Gary L Westbrook, David Lutz, Michael Frotscher
Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone...
January 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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