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https://www.readbyqxmd.com/read/28087635/rb-controls-growth-survival-and-neuronal-migration-in-human-cerebral-organoids
#1
Takeshi Matsui, Vanesa Nieto-Estévez, Sergii Kyrychenko, Jay W Schneider, Jenny Hsieh
Retinoblastoma (RB) is a tumor suppressor gene which regulates cell cycle entry to S phase via E2F transcription factors. Using knockout (KO) mice, it has been described that Rb plays a role in cell migration and differentiation in developing and adult brain as well as apoptosis. In addition, the RB family is required for the self-renewal and survival of human embryonic stem cells (ESCs). However, little is known about the role of this gene in human brain development. Here, we investigated the role of RB in cerebral organoids from human ESCs deficient for RB...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28039900/evidence-of-early-defects-in-cajal-retzius-cell-localisation-during-brain-development-in-a-mouse-model-of-dystroglycanopathy
#2
H S Booler, V Pagalday-Vergara, J L Williams, M Hopkinson, S C Brown
AIMS: The secondary dystroglycanopathies represent a heterogeneous group of congenital muscular dystrophies characterised by the defective glycosylation of alpha dystroglycan. These disorders are associated with mutations in at least 17 genes, including Fukutin-related protein (FKRP). At the severe end of the clinical spectrum there is substantial brain involvement, and cobblestone lissencephaly is highly suggestive of these disorders. The precise pathogenesis of this phenotype has however, remained unclear with most attention focused on the disruption to the radial glial scaffold...
December 31, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/27994051/reelin-neurodevelopmental-architect-and-homeostatic-regulator-of-excitatory-synapses
#3
Catherine R Wasser, Joachim Herz
Over half a century ago, D.S. Falconer first reported a mouse with a reeling gate (1). Four-decades later, the Reln gene was isolated and identified as the cause of the reeler phenotype (reviewed in (2)). Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Reln gene, results in abnormal neuronal layering throughout several regions of the brain (reviewed in (2-4)). In the years since, the known functions of Reelin signaling in the brain have expanded to include multiple post-developmental neuromodulatory roles, revealing an ever-increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation of synaptic function (reviewed in (5))...
December 19, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27986930/c-terminal-region-truncation-of-reln-disrupts-an-interaction-with-vldlr-causing-abnormal-development-of-the-cerebral-cortex-and-hippocampus
#4
Seungshin Ha, Prem P Tripathi, Anca B Mihalas, Robert F Hevner, David R Beier
: We discovered a hypomorphic reelin (Reln) mutant with abnormal cortical lamination and no cerebellar hypoplasia. This mutant, Reln (CTRdel), carries a chemically-induced splice-site mutation that truncates the C-terminal region (CTR) domain of RELN protein and displays remarkably distinct phenotypes from reeler The mutant does not have an inverted cortex, but cortical neurons overmigrate and invade the marginal zone, which is similar to a phenotype seen in the cerebral cortex of Vldlr (null) mice...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27915032/reelin-expression-is-up-regulated-in-mice-colon-in-response-to-acute-colitis-and-provides-resistance-against-colitis
#5
Ana E Carvajal, María D Vázquez-Carretero, Pablo García-Miranda, María J Peral, María L Calonge, Anunciación A Ilundain
Reelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the reelin signalling system; its response to dextran sulphate sodium (DSS) and the response of wild-type and reeler mice to DSS-treatment. DNA methylation was determined by bisulfite modification and sequencing of genomic DNA...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27909010/apoer2-controls-not-only-neuronal-migration-in-the-intermediate-zone-but-also-termination-of-migration-in-the-developing-cerebral-cortex
#6
Yuki Hirota, Ken-Ichiro Kubo, Takahiro Fujino, Tokuo T Yamamoto, Kazunori Nakajima
Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27882975/ephrin-bs-and-canonical-reelin-signalling
#7
Theresa Pohlkamp, Lei Xiao, Rukhsana Sultana, Asim Bepari, Hans H Bock, Mark Henkemeyer, Joachim Herz
No abstract text is available yet for this article.
24, 2016: Nature
https://www.readbyqxmd.com/read/27866325/sexually-dimorphic-expression-of-reelin-in-the-brain-of-a-mouse-model-of-alzheimer-disease
#8
Giampiero Palladino, Vincenzina Nicolia, Gabor G Kovacs, Sonia Canterini, Viviana Ciraci, Andrea Fuso, Franco Mangia, Sigfrido Scarpa, Maria Teresa Fiorenza
Recent evidence highlights the protective role of reelin against amyloid β (Aβ)-induced synaptic dysfunction and cognitive impairment in Alzheimer disease (AD). In this study, exploiting TgCRND8 mice that overexpress a mutant form of amyloid β precursor protein (AβPP) and display an early onset of AD neuropathological signs, we addressed the question whether changes of reelin expression eventually precede the appearance of Aβ-plaques in a sex-dependent manner. We show that sex-associated and brain region-specific differences in reelin expression appear long before Aβ-plaque formation...
November 19, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27865768/regulation-of-extrasynaptic-signaling-by-polysialylated-ncam-impact-for-synaptic-plasticity-and-cognitive-functions
#9
REVIEW
Hristo Varbanov, Alexander Dityatev
The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for induction of synaptic plasticity and supports cell survival, whereas activation of extrasynaptic NMDARs inhibits long-term potentiation and triggers neurodegeneration. A soluble polysialylated form of the neural cell adhesion molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B-containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism result in impaired synaptic plasticity and learning, which could be repaired by reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or downstream signaling through RasGRF1 and p38 MAP kinase...
November 16, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27843148/hypervulnerability-of-the-adolescent-prefrontal-cortex-to-nutritional-stress-via-reelin-deficiency
#10
M A Labouesse, O Lassalle, J Richetto, J Iafrati, U Weber-Stadlbauer, T Notter, T Gschwind, L Pujadas, E Soriano, A C Reichelt, C Labouesse, W Langhans, P Chavis, U Meyer
Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN(+) cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits...
November 15, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27810638/presenilin-1-mutations-influence-processing-and-trafficking-of-the-apoe-receptor-apoer2
#11
Wei Wang, Andrea M Moerman-Herzog, Arthur Slaton, Steven W Barger
Presenilin (PS)-1 is an intramembrane protease serving as the catalytic component of γ-secretase. Mutations in the PS1 gene are the most common cause of familial Alzheimer's disease (FAD). The low-density lipoprotein (LDL)-receptor family member apoER2 is a γ-secretase substrate that has been associated with AD in several ways, including acting as a receptor for apolipoprotein E (ApoE). ApoER2 is processed by γ-secretase into a C-terminal fragment (γ-CTF) that appears to regulate gene expression. FAD PS1 mutations were tested for effects on apoER2...
January 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27803648/reelin-and-neuropsychiatric-disorders
#12
REVIEW
Kazuhiro Ishii, Ken-Ichiro Kubo, Kazunori Nakajima
Proper neuronal migration and laminar formation during corticogenesis is essential for normal brain function. Disruption of these developmental processes is thought to be involved in the pathogenesis of some neuropsychiatric conditions. Especially, Reelin, a glycoprotein mainly secreted by the Cajal-Retzius cells and a subpopulation of GABAergic interneurons, has been shown to play a critical role, both during embryonic and postnatal periods. Indeed, animal studies have clearly revealed that Reelin is an essential molecule for proper migration of cortical neurons and finally regulates the cell positioning in the cortex during embryonic and early postnatal stages; by contrast, Reelin signaling is closely involved in synaptic function in adulthood...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27765946/multivariate-synaptic-and-behavioral-profiling-reveals-new-developmental-endophenotypes-in-the-prefrontal-cortex
#13
Jillian Iafrati, Arnaud Malvache, Cecilia Gonzalez Campo, M Juliana Orejarena, Olivier Lassalle, Lamine Bouamrane, Pascale Chavis
The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice...
October 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27739126/non-neuronal-roles-for-the-reelin-signaling-pathway
#14
Elvira Khialeeva, Ellen M Carpenter
The reelin signaling pathway has been established as an important regulator of cell migration during development of the central nervous system, and disruptions in reelin signaling alter the positioning of many types of neurons in the developing central nervous system. Reelin is a large extracellular matrix glycoprotein and governs cell migration through activation of multiple intracellular signaling events via the receptors ApoE receptor 2 (ApoER2) and Very Low Density Lipoprotein Receptor (VLDLR), and the intracellular adaptor protein Disabled-1 (Dab1)...
October 14, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27735078/the-effects-of-prenatal-h1n1-infection-at-e16-on-fmrp-glutamate-gaba-and-reelin-signaling-systems-in-developing-murine-cerebellum
#15
S Hossein Fatemi, Timothy D Folsom, Stephanie B Liesch, Rachel E Kneeland, Mahtab Karkhane Yousefi, Paul D Thuras
Prenatal viral infection has been identified as a potential risk factor for the development of neurodevelopmental disorders such as schizophrenia and autism. Additionally, dysfunction in gamma-aminobutyric acid, Reelin, and fragile X mental retardation protein (FMRP)-metabotropic glutamate receptor 5 signaling systems has also been demonstrated in these two disorders. In the current report, we have characterized the developmental profiles of selected markers for these systems in cerebella of mice born to pregnant mice infected with human influenza (H1N1) virus on embryonic day 16 or sham-infected controls using SDS-PAGE and Western blotting techniques and evaluated the presence of abnormalities in the above-mentioned markers during brain development...
October 13, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27726110/reelin-expression-in-creutzfeldt-jakob-disease-and-experimental-models-of-transmissible-spongiform-encephalopathies
#16
Agata Mata, Laura Urrea, Silvia Vilches, Franc Llorens, Katrin Thüne, Juan-Carlos Espinosa, Olivier Andréoletti, Alejandro M Sevillano, Juan María Torres, Jesús Rodríguez Requena, Inga Zerr, Isidro Ferrer, Rosalina Gavín, José Antonio Del Río
Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease...
October 10, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27720810/impaired-fear-extinction-retention-and-increased-anxiety-like-behaviours-induced-by-limited-daily-access-to-a-high-fat-high-sugar-diet-in-male-rats-implications-for-diet-induced-prefrontal-cortex-dysregulation
#17
Kathryn D Baker, Amy C Reichelt
Anxiety disorders and obesity are both common in youth and young adults. Despite increasing evidence that over-consumption of palatable high-fat/high-sugar "junk" foods leads to adverse neurocognitive outcomes, little is known about the effects of palatable diets on emotional memories and fear regulation. In the present experiments we examined the effects of daily 2h consumption of a high-fat/high-sugar (HFHS) food across adolescence on fear inhibition and anxiety-like behaviour in young adult rats. Rats exposed to the HFHS diet exhibited impaired retention of fear extinction and increased anxiety-like behaviour in an emergence test compared to rats fed a standard diet...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27703495/identification-of-hub-genes-and-pathways-associated-with-hepatocellular-carcinoma-based-on-network-strategy
#18
Jun Liu, Ping Hua, Li Hui, Li-Li Zhang, Zhen Hu, Ying-Wei Zhu
The objective of this study was to identify hub genes and pathways associated with hepatocellular carcinoma (HCC) by centrality analysis of a co-expression network. A co-expression network based on differentially expressed (DE) genes of HCC was constructed using the Differentially Co-expressed Genes and Links (DCGL) package. Centrality analyses, for centrality of degree, clustering coefficient, closeness, stress and betweenness for the co-expression network were performed to identify hub genes, and the hub genes were combined together to overcome inconsistent results...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27624722/reelin-regulates-the-maturation-of-dendritic-spines-synaptogenesis-and-glial-ensheathment-of-newborn-granule-cells
#19
Carles Bosch, Nuria Masachs, David Exposito-Alonso, Albert Martínez, Cátia M Teixeira, Isabel Fernaud, Lluís Pujadas, Fausto Ulloa, Joan X Comella, Javier DeFelipe, Angel Merchán-Pérez, Eduardo Soriano
: The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons...
September 13, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27602387/schizophrenia-patient-derived-olfactory-neurosphere-derived-cells-do-not-respond-to-extracellular-reelin
#20
Jing Yang Tee, Ratneswary Sutharsan, Yongjun Fan, Alan Mackay-Sim
Reelin expression is reduced in various regions in the post-mortem brain of schizophrenia patients but the exact role of reelin function in the neurobiology of schizophrenia remains elusive. Absence of reelin in knockout mouse causes inverted lamination of the neocortex due to aberrant neuronal migration. The aim of this study was to utilize patient-derived olfactory neurosphere-derived (ONS) cells to investigate whether extracellular reelin alters cell motility in schizophrenia patient-derived cells. ONS cells from nine patients were compared with cells from nine matched healthy controls...
2016: NPJ Schizophrenia
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