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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
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
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
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...
October 5, 2016: Neurobiology of Learning and Memory
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
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
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
Pablo Vázquez-Borsetti, Elena Peña, Catalina Rico, Mariana Noto, Nathalie Miller, Diego Cohon, Juan Manuel Acosta, Mariano Ibarra, Fabián C Loidl
Obstetrical complications of perinatal asphyxia (PA) can often induce lesions that, in the long-term, manifest as schizophrenia. A deterioration of the medial prefrontal cortex (mPFC) and a reduction in the number of GABAergic neurons are commonly observed in the pathophysiology of schizophrenia. In this study, we investigated the link between PA, reelin and calbindin diminution and psychiatric diseases that involve social interaction deficits. This was achieved by observing the effect of 19 min of asphyxia on both subpopulations of GABAergic neurons...
September 6, 2016: Developmental Neuroscience
Kota Nakamura, Mako Beppu, Kaori Sakai, Hayata Yagyu, Saori Matsumaru, Takao Kohno, Mitsuharu Hattori
In the normal cerebellum, Purkinje cells (PCs) are generated in a zone along the ventricular surface, migrate radially, and align to form a single-cell layer. However, in mice lacking the secreted protein Reelin or its downstream adaptor protein Dab1, the majority of PCs are located ectopically in the deep cerebellar mass. Nonetheless, how Reelin regulates migration and alignment of PCs remains incompletely understood. Reelin has a highly-conserved C-terminal region (CTR), which is required for its full activity...
November 12, 2016: Neuroscience
Alessia Luoni, Peter Gass, Paolo Brambilla, Mirella Ruggeri, Marco A Riva, Dragos Inta
The evidence underlying the so-called glutamatergic hypothesis ranges from NMDA receptor hypofunction to an imbalance between excitatory and inhibitory circuits in specific brain structures. Among all glutamatergic system components, metabotropic receptors play a main role in regulating neuronal excitability and synaptic plasticity. Here, we investigated, using qRT-PCR and western blot, consequences in the hippocampus and prefrontal/frontal cortex (PFC/FC) of mice with a genetic deletion of the metabotropic glutamate receptor 5 (mGlu5), addressing key components of the GABAergic and glutamatergic systems...
August 31, 2016: European Archives of Psychiatry and Clinical Neuroscience
Esmat Fathi, Fatemeh Hedayati Katouli, Gholam Hossein Riazi, Marzieh Dehghan Shasaltaneh, Elham Parandavar, Samaneh Bayati, Ali Afrasiabi, Reza Nazari
Reelin is an extracellular glycoprotein which contributes to synaptic plasticity and function of memory in the adult brain. It has been indicated that the Reelin signaling cascade participates in Alzheimer's disease (AD). Besides the neurons, glial cells such as astrocytes also express Reelin protein. While functional loss of astrocytes has been reported to be associated with AD, dysfunction of astrocytic Reelin signaling pathway has not received much attention. Therefore, we investigated the effects of α-boswellic acid (ABA) as one of the major component of Boswellia serrata resin on primary fetal human astrocytes under a stress paradigm as a possible model for AD through study on Reelin cascade...
August 27, 2016: Neuromolecular Medicine
Yousuke Watanabe, Tomoaki Murakami, Masashi Kawashima, Yasuko Hasegawa-Baba, Sayaka Mizukami, Nobuya Imatanaka, Yumi Akahori, Toshinori Yoshida, Makoto Shibutani
Valproic acid (VPA) is used to establish models of experimental autism. The present study investigated the developmental exposure effect of VPA on postnatal hippocampal neurogenesis in accordance with the exposure scheme of OECD Test Guideline 426 adopted for developmental neurotoxicity. Pregnant rats were administered drinking water containing 0, 667, or 2000 ppm VPA from gestational day 6 until day 21 post-delivery. In the subgranular zone (SGZ) and granule cell layer (GCL) of offspring, the number of granule cell lineage subpopulations remained unchanged upon weaning...
August 26, 2016: Neurotoxicity Research
Marina Bučić, Peter Pregelj, Tomaž Zupanc, Alja Videtič Paska
OBJECTIVE: Suicidal behavior is a complex phenomenon, an outcome of both environmental and genetic factors. In the present study, we looked for a potential association between suicide and the reelin gene as reelin has been associated previously with several psychiatric disorders, including depression. MATERIALS AND METHODS: We analyzed three single nucleotide polymorphisms (SNPs) in the reelin gene, rs2965087, rs7341475, and rs362691, in a population of 483 suicide victims and 332 healthy controls, all Caucasians...
October 2016: Psychiatric Genetics
Inmaculada Cuchillo-Ibañez, Trinidad Mata-Balaguer, Valeria Balmaceda, Juan José Arranz, Johannes Nimpf, Javier Sáez-Valero
Reelin is a signaling protein that plays a crucial role in synaptic function, which expression is influenced by β-amyloid (Aβ). We show that Reelin and Aβ oligomers co-immunoprecipitated in human brain extracts and were present in the same size-exclusion chromatography fractions. Aβ treatment of cells led to increase expression of Reelin, but secreted Reelin results trapped together with Aβ aggregates. In frontal cortex extracts an increase in Reelin mRNA, and in soluble and insoluble (guanidine-extractable) Reelin protein, was associated with late Braak stages of Alzheimer's disease (AD), while expression of its receptor, ApoER2, did not change...
2016: Scientific Reports
Catarina Orcinha, Gert Münzner, Johannes Gerlach, Antje Kilias, Marie Follo, Ulrich Egert, Carola A Haas
Granule cell dispersion (GCD) represents a pathological widening of the granule cell layer in the dentate gyrus and it is frequently observed in patients with mesial temporal lobe epilepsy (MTLE). Recent studies in human MTLE specimens and in animal epilepsy models have shown that a decreased expression and functional inactivation of the extracellular matrix protein Reelin correlates with GCD formation, but causal evidence is still lacking. Here, we used unilateral kainate (KA) injection into the mouse hippocampus, an established MTLE animal model, to precisely map the loss of reelin mRNA-synthesizing neurons in relation to GCD along the septotemporal axis of the epileptic hippocampus...
2016: Frontiers in Cellular Neuroscience
Kazunori Nakajima
Reelin controls the neuronal layer formation in the developing cerebral neocortex. The Reelin glycoprotein is mainly secreted from Cajal-Retzius cells in the marginal zone, and it guides the proper aggregation of the migrating neurons in a birth-dependent "inside-out" manner. Reelin also regulates the final process of neuronal migration (terminal translocation and somal translocation) by activating integrin and N-cadherin. It is also expressed around the subventricular zone and it controls the behavior of the migrating neurons...
August 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
A Micera, B O Balzamino, F Biamonte, G Esposito, R Marino, F Fanelli, F Keller
Reelin is a matrix glycoprotein that plays a pivotal role for the positioning of neurons throughout brain development. In the early developing cortex Reelin regulates radial migration of cortical neurons while later in development, Reelin promotes maturation of dendrites and dendritic spines. Low Reelin levels characterize healthy adult brain while increased Reelin levels have been associated with cellular events underlying response to injury. Reelin has been detected in structural and immune cells outside brain (liver, gut/colon tracts, kidney, testis, ovary, lung, retina and cornea)...
August 5, 2016: Current Molecular Medicine
Jiang Xie, Hua Li, Hua Zhu, Li Huang, Hongxia Li, Xiling Zhang, Yongmei Zhou, Qiang Zhou, Wenming Xu
OBJECTIVE: To analyze the clinical manifestations and gene mutation of a 6 year old boy with autism spectrum disorders (ASD). METHODS: Peripheral blood of the boy and his parents were subjected to genetic testing. RESULTS: The patient was diagnosed with typical autism. Exome sequencing has identified mutations of four candidate genes, namely TUT1, DIAPH3, REELIN and SETD2, which were confirmed with Sanger sequencing. Analysis of family members confirmed that the missense mutations of DIAPH3 and SETD2 genes were of de novo origin...
August 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Jayakumar Preethi, Hemant K Singh, Koilmani E Rajan
Bacopa monniera extract (CDRI-08; BME) has been known to improve learning and memory, and understanding the molecular mechanisms may help to know its specificity. We investigated whether the BME treatment alters the methylation status of reelin and brain-derived neurotropic factor (BDNF) to enhance the memory through the interaction of N-methyl-D-aspartate receptor (NMDAR) with synaptic proteins. Rat pups were subjected to novel object recognition test following daily oral administration of BME (80 mg/kg) in 0...
2016: Frontiers in Pharmacology
Hans H Bock, Petra May
Reelin is a large secreted glycoprotein that is essential for correct neuronal positioning during neurodevelopment and is important for synaptic plasticity in the mature brain. Moreover, Reelin is expressed in many extraneuronal tissues; yet the roles of peripheral Reelin are largely unknown. In the brain, many of Reelin's functions are mediated by a molecular signaling cascade that involves two lipoprotein receptors, apolipoprotein E receptor-2 (Apoer2) and very low density-lipoprotein receptor (Vldlr), the neuronal phosphoprotein Disabled-1 (Dab1), and members of the Src family of protein tyrosine kinases as crucial elements...
2016: Frontiers in Cellular Neuroscience
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