DOCSLIB.ORG

General Summary

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
General Summary Molecular Psychiatry (2005) 10, 227–228 & 2005 Nature Publishing Group All rights reserved 1359-4184/05 $30.00 www.nature.com/mp General Summary A Midei and J Licinio UCLA, Los Angeles, CA, USA Molecular Psychiatry (2005) 10, 227–228. doi:10.1038/sj.mp.4001651 SCIENTIFIC CORRESPONDENCE evidence for association between a gene that maps to 15q, called dyslexia susceptibility 1 candidate 1 Tree pollen peaks are associated with increased (DYX1C1 or EKN1). However, the findings in each nonviolent suicide in women study are somewhat contradictory. The authors TT Postolache, JW Stiller, R Herrell, MA Goldstein, examined the critical markers from the previous SS Shreeram, R Zebrak, CM Thrower, J Volkov, studies in an attempt to replicate either study. The MJ No, I Volkov, KJ Rohan, J Redditt, M Parmar, data provided no support for association, and when F Mohyuddin, C Olsen, M Moca, LH Tonelli, considered in the context of the existing evidence, the K Merikangas, HD Komarow authors concluded that DYX1C1 is unlikely to be a susceptibility gene for DD. Postolache et al. hypothesized that seasonal environ- mental factors, which cause inflammation and cyto- kine release, such as infection and allergy, contribute TEN YEARS OF MOLECULAR PSYCHIATRY to the highly replicated but poorly explained seasonal peaks of suicide. In a large US-wide epidemiological Brain–immune interactions and disease susceptibility study, the authors reported a greater rate of nonviolent A Marques-Deak, G Cizza, E Sternberg suicides during and after high tree-pollen periods. This finding is consistent with the previously Many studies have established the routes by which reported association between allergy and depression the immune and central nervous systems (CNS) in women but not in men. communicate. This network of connections permits a bidirectional regulation of the immune and Absence of psychosis may influence linkage results CNS systems, playing an important role in suscep- for bipolar disorder tibility and resistance to autoimmune, inflammatory, N Park, R Cheng, SH Juo, J Liu, JE Loth, J Endicott, infectious, and allergic diseases. This review focused TC Gilliam, M Baron on the regulation of the immune system via the neuroendocrine system, and underscored the link Genome-wide linkage analysis was carried out in between neuroendocrine dysregulation and develop- pedigrees with bipolar disorder (BP). The analysis ment of major depressive disorders, autoimmune focused on BP with no psychotic features (nonpsy- diseases, and osteoporosis. chotic BP). Support for linkage was observed on chromosomes 1p35, 3p14, 3q13, 6q24, and 8q24. Reelin glycoprotein: structure, biology and roles in These regions differ from those implicated in a health and disease previous study, which focused on BP with psychosis SH Fatemi (psychotic BP). The results suggest that some psycho- tic and nonpsychotic varieties of BP may be governed Reelin glycoprotein is a secretory serine protease, by different susceptibility loci. with dual roles in the mammalian brain: embryologi- cally, it guides neurons and radial glial cells to their No support for association between Dyslexia Suscep- corrected positions in the developing brain; in adult tibility 1 Candidate 1 and developmental dyslexia brain, Reelin is involved in a signaling pathway, NA Cope, G Hill, M van den Bree, D Harold, which underlies neurotransmission, memory forma- V Moskvina, EK Green, MJ Owen, J Williams, tion, and synaptic plasticity. Disruption of the Reelin MC O’Donovan signaling pathway by mutations and selective hyper- methylation of the Reelin gene promoter or following Several candidate chromosomal regions have been various pre- or postnatal insults may lead to cognitive identified for developmental dyslexia (DD) including deficits present in neuropsychiatric disorders like chromosome 15q. Recently, two groups have provided autism or schizophrenia. General Summary 228 Obsessive-compulsive disorder phenotypes: implica- Wisconsin Card Sorting, Digit Span backward, and tions for genetic studies Trail Making tests, as well as MRI frontal brain EC Miguel, JF Leckman, S Rauch, MC do Rosario- volumes and PET frontal cerebral blood flow. Campos, AG Hounie, MT Mercadante, P Chacon, Although the complex genetics and phenotypic DL Pauls heterogeneity of schizophrenia remain as major obstacles toward elucidating its underlying neuro- This review proposed several different approaches to biology, integrating multimodal investigational ap- understand the complexity of the OCD phenotype proaches from cognitive neurosciences and molecular including: (1) narrowing the phenotype to identify genetics can help address these challenges in schizo- categorically defined more homogeneous and mutu- phrenia research. ally exclusive subtypes of OCD; (2) considering OC symp- tom dimensions as quantitative components of the Influenza A virus infection causes alterations in more complex OCD phenotype; and (3) broadening expression of synaptic regulatory genes combined the phenotype to include other etiologically related with changes in cognitive and emotional behaviors conditions. A combined dimensional approach in mice within distinctive subgroups was proposed as most S Beraki, F Aronsson, H Karlsson, SO O¨gren, effective in helping to identify the heritable compo- K Kristensson nents of OCD. Viral infections have been suggested to be responsible for a number of complex human disorders including ORIGINAL RESEARCH ARTICLES schizophrenia. In the present study, influenza A virus was injected into the brains of C57BL/6 mice. Long Inhibition of System A-mediated glycine transport in after this nonlethal infection had been cleared these cortical synaptosomes by therapeutic concentrations animals exhibited disturbances in cognitive and of clozapine: implications for mechanisms of action emotional functions. These were accompanied by DC Javitt, L Duncan, A Balla, H Sershen alterations in the transcriptional activity of genes involved in synaptic transmission as compared to Clozapine is an atypical antipsychotic with particular control mice. Thus, infections targeting the brain may efficacy in schizophrenia. This study investigated the cause persistent changes in gene expression com- possibility that clozapine may produce its unique bined with behavioral disturbances. effects by blocking brain glycine reuptake, thereby stimulating N-methyl-D-aspartate (NMDA) receptor- Transcriptional profiling reveals evidence for dependent neurotransmission. Two glycine transport signaling and oligodendroglial abnormalities in the processes were identified in brain synaptosomes, temporal cortex from patients with major depressive corresponding to the properties of the glycine type I disorder (9GLYT1) and system A (SNAT2) transporters, respec- C Aston, L Jiang, BP Sokolov tively. Clozapine significantly inhibited glycine trans- port via the system A-mediated system, suggesting that it may significantly regulate glycine levels in vivo. Microarray analysis revealed significant changes in expression of genes involved in neurodevelopment, signal transduction, and cell communication in Catechol-O-methyl transferase Val158Met gene temporal cortex from patients with major depression. polymorphism in schizophrenia: working memory, Among these, the expression of multiple oligoden- frontal lobe MRI morphology and frontal cerebral droglia- and axonal growth/synaptic function-related blood flow genes was altered. These findings indicate that major B-C Ho, TH Wassink, DS O’Leary, VC Sheffield, depression is associated with altered cell commu- NC Andreasen nication and signal transduction mechanisms that contribute to abnormalities in oligodendroglia and The authors failed to find significant genotype effects synaptic function. The data also suggest that major on a wide range of frontal lobe-related measures: depression shares common oligodendroglial abnorm- working memory/executive functions assessed using alities with schizophrenia and bipolar disorder. Molecular Psychiatry.
Load more

Recommended publications
  • Reelin Is Preferentially Expressed in Neurons Synthesizing ␥-Aminobutyric Acid in Cortex and Hippocampus of Adult Rats
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 3221–3226, March 1998 Neurobiology Reelin is preferentially expressed in neurons synthesizing g-aminobutyric acid in cortex and hippocampus of adult rats C. PESOLD*†,F.IMPAGNATIELLO*, M. G. PISU*, D. P. UZUNOV*, E. COSTA*, A. GUIDOTTI*, AND H. J. CARUNCHO*‡ *Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; and ‡Department of Morphological Sciences, University of Santiango de Compostela School of Medicine, 15705 Santiago de Compostela, Spain Contributed by Erminio Costa, December 24,1997 ABSTRACT During embryonic development of brain lam- sion, prevent Reelin transcription or secretion (4, 12, 14). In inated structures, the protein Reelin, secreted into the extracel- the cortex and hippocampus of rat embryos, Reelin begins to lular matrix of the cortex and hippocampus by Cajal–Retzius be synthesized in Cajal–Retzius (CR) cells from embryonic day (CR) cells located in the marginal zone, contributes to the 13 to the second postnatal week, and in the cerebellum Reelin regulation of migration and positioning of cortical and hip- is expressed first in the external granule cell layer (EGL) pocampal neurons that do not synthesize Reelin. Soon after before the granule cell migration to the internal granule cell birth, the CR cells decrease, and they virtually disappear during layer (IGL) (2, 15–17). When the CR50 antibody is added to the following 3 weeks. Despite their disappearance, we can embryonic preparations expressing normal histogenetic pat- quantify Reelin mRNA (approximately 200 amolymg of total terns of lamination, it induces typical histogenetic abnormal- RNA) and visualize it by in situ hybridization, and we detect the ities of the Relnrl phenotype (7, 9, 10, 17).
    [Show full text]
  • Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders
    fncel-14-00285 August 31, 2020 Time: 14:32 # 1 ORIGINAL RESEARCH published: 02 September 2020 doi: 10.3389/fncel.2020.00285 Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders Daisuke Ibi1*†, Genki Nakasai1†, Nayu Koide1†, Masahito Sawahata2, Takao Kohno3, Rika Takaba1, Taku Nagai2,4, Mitsuharu Hattori3, Toshitaka Nabeshima5, Kiyofumi Yamada2* and Masayuki Hiramatsu1 1 Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan, 2 Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan, 3 Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan, 4 Project Office for Neuropsychological Research Center, Fujita Health University, Toyoake, Japan, 5 Advanced Diagnostic System Research Laboratory, Fujita Health University, Graduate School of Health Sciences, Toyoake, Japan Edited by: Marie-Eve Tremblay, In the majority of schizophrenia patients, chronic atypical antipsychotic administration University of Victoria, Canada produces a significant reduction in or even complete remission of psychotic symptoms Reviewed by: such as hallucinations and delusions. However, these drugs are not effective in Dilja Krueger-Burg, improving cognitive and emotional deficits in patients with schizophrenia. Atypical University Medical Center Göttingen, Germany antipsychotic drugs have a high affinity for the dopamine D2 receptor, and a José M. Delgado-García,
    [Show full text]
  • Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders
    Hindawi Publishing Corporation Autism Research and Treatment Volume 2012, Article ID 868576, 6 pages doi:10.1155/2012/868576 Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders Naghi Momeni,1 Lars Brudin,2 Fatemeh Behnia,3 Berit Nordstrom,¨ 4 Ali Yosefi-Oudarji,5 Bengt Sivberg,4 Mohammad T. Joghataei,5 and Bengt L. Persson1 1 School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden 2 Department of Clinical Physiology, Kalmar County Hospital, 39185 Kalmar, Sweden 3 Department of Occupational Therapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran 4 Department of Health Sciences, Autism Research, Faculty of Medicine, Lund University, Box 157, 22100 Lund, Sweden 5 Cellular and Molecular Research Centre, Tehran University of Medical Sciences (TUMS), Tehran, Iran Correspondence should be addressed to Bengt Sivberg, [email protected] Received 17 June 2011; Revised 22 August 2011; Accepted 22 August 2011 Academic Editor: Judy Van de Water Copyright © 2012 Naghi Momeni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Im- mune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine pro- tease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system.
    [Show full text]
  • Reelin Gene Polymorphisms in Autistic Disorder
    Chapter 25 Reelin Gene Polymorphisms in Autistic Disorder Carla Lintas and Antonio Maria Persico Contents 1 Introduction ....................................................................................................................... 385 2 RELN Gene Polymorphisms and Autism .......................................................................... 386 3 Functional Studies of RELN GGC Alleles ........................................................................ 389 4 RELN GGC Alleles and Autism: Replication Studies ....................................................... 390 5 Modeling RELN Gene Contributions to Autism: The Challenge of Complexity .............. 394 References ............................................................................................................................... 396 1 Introduction Migratory streams occur throughout the central nervous system (CNS) during devel- opment. Neuronal and glial cell populations migrate out of proliferative zones to reach their final location, where neurons soon establish early intercellular connec- tions. Reelin plays a pivotal role in cell migration processes, acting as a stop signal for migrating neurons in several CNS districts, including the neocortex, the cerebel- lum, and the hindbrain (Rice and Curran, 2001). At the cellular level, Reelin acts by binding to a variety of receptors, including the VLDL receptors, ApoER2, and α3β1 integrins, and also by exerting a proteolytic activity on extracellular matrix proteins, which is critical to neuronal migration
    [Show full text]
  • Reelin, a Marker of Stress Resilience in Depression and Psychosis
    Neuropsychopharmacology (2011) 36, 2371–2372 & 2011 American College of Neuropsychopharmacology. All rights reserved 0893-133X/11 www.neuropsychopharmacology.org Commentary Reelin, a Marker of Stress Resilience in Depression and Psychosis ,1,2 S Hossein Fatemi* 1 2 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA; Departments of Neuroscience and Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA Neuropsychopharmacology (2011) 36, 2371–2372; doi:10.1038/npp.2011.169 Reelin protein is an extracellular matrix protease respon- common phenomena subserving cognitive deficits in multi- sible for normal lamination of the brain during embryo- ple disorders including lissencephaly, Alzheimer’s disease, genesis, and is involved in cell signaling and synaptic and temporal lobe epilepsy. The causative factors may plasticity in adult life. The Reelin gene (RELN) is localized include a mutation in the RELN gene (lissencephaly) to to chromosome 7 in humans and chromosome 5 in mice, variable expression of the molecule due to hypermethylation and produces a protein product with relative molecular of the promoter region of the RELN gene or other unknown mass of 388 kDa. Reelin protein is localized to a number of mechanisms. Moreover, several non-CNS disorders have brain sites, specifically Cajal–Retzius cells located in layer 1 been associated with changes in expression of Reelin of neocortex, GABAergic interneurons, and cerebellar including several forms of cancers and otosclerosis. granule cells. Activation of the Reelin signaling pathway In the current issue, Teixeira and colleagues evaluated the leads to various, important functions such as enhancement effects of overexpression of Reelin in a transgenic mouse of long-term potentiation, cell proliferation, cell migration, model as compared with wild-type mice and to hetero- and more importantly dendritic spine morphogenesis.
    [Show full text]
  • Plasminogen Activator Inhibitor 1 Functions As a Urokinase Response Modifier at the Level of Cell Signaling and Thereby Promotes MCF-7 Cell Growth Donna J
    Plasminogen Activator Inhibitor 1 Functions as a Urokinase Response Modifier at the Level of Cell Signaling and Thereby Promotes MCF-7 Cell Growth Donna J. Webb, Keena S. Thomas, and Steven L. Gonias Department of Pathology, and Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908 Abstract. Plasminogen activator inhibitor 1 (PAI-1) is association of Sos with Shc, whereas uPA caused tran- Downloaded from http://rupress.org/jcb/article-pdf/152/4/741/1297334/0011017.pdf by guest on 28 September 2021 a major inhibitor of urokinase-type plasminogen activa- sient association of Sos with Shc. tor (uPA). In this study, we explored the role of PAI-1 By sustaining ERK phosphorylation, PAI-1 con- in cell signaling. In MCF-7 cells, PAI-1 did not directly verted uPA into an MCF-7 cell mitogen. This activity activate the mitogen-activated protein (MAP) kinases, was blocked by receptor-associated protein and not ob- extracellular signal–regulated kinase (ERK) 1 and served with uPA–PAI-1R76E complex, demonstrating ERK2, but instead altered the response to uPA so the importance of the VLDLr. uPA promoted the that ERK phosphorylation was sustained. This effect growth of other cells in which ERK phosphorylation required the cooperative function of uPAR and the was sustained, including ␤3 integrin overexpressing very low density lipoprotein receptor (VLDLr). When MCF-7 cells and HT 1080 cells. The MEK inhibitor, MCF-7 cells were treated with uPA–PAI-1 complex in PD098059, blocked the growth-promoting activity of the presence of the VLDLr antagonist, receptor-associ- uPA and uPA–PAI-1 complex in these cells.
    [Show full text]
  • Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy
    The Journal of Neuroscience, July 15, 2002, 22(14):5797–5802 Brief Communication Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy Carola A. Haas,1 Oliver Dudeck,2 Matthias Kirsch,1 Csaba Huszka,1 Gunda Kann,1 Stefan Pollak,3 Josef Zentner,2 and Michael Frotscher1 1Institute of Anatomy, 2Department of Neurosurgery, and 3Institute of Forensic Medicine, University of Freiburg, D-79001 Freiburg, Germany The reelin signaling pathway plays a crucial role during the lobe epilepsy. These results suggest that reelin is required for development of laminated structures in the mammalian brain. normal neuronal lamination in humans, and that deficient reelin Reelin, which is synthesized and secreted by Cajal–Retzius expression may be involved in migration defects associated cells in the marginal zone of the neocortex and hippocampus, is with temporal lobe epilepsy. proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hip- Key words: human hippocampus; extracellular matrix; neuro- pocampal Cajal–Retzius cells correlates with the extent of mi- nal migration disorder; Cajal–Retzius cells; dentate gyrus; Am- gration defects in the dentate gyrus of patients with temporal mon’s horn sclerosis Newborn forebrain neurons migrate from their site of origin to reelin pathway underlie neuronal migration defects in reeler mu- their definitive positions in the cortical plate. Defects in neuronal tants and in humans with TLE. migration are often associated with epileptic disorders (Palmini et To this end, we have studied the expression of reelin, VLDLR, al., 1991). Temporal lobe epilepsy (TLE), one of the most com- ApoER2, and dab1 in tissue samples of hippocampus removed mon neurological disorders in humans (Margerison and Corsellis, from TLE patients for therapeutic reasons.
    [Show full text]
  • Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis
    4776 • The Journal of Neuroscience, March 18, 2015 • 35(11):4776–4787 Cellular/Molecular Importance of Reelin C-Terminal Region in the Development and Maintenance of the Postnatal Cerebral Cortex and Its Regulation by Specific Proteolysis Takao Kohno,1* Takao Honda,2* Ken-ichiro Kubo,2* Yoshimi Nakano,1 Ayaka Tsuchiya,1 Tatsuro Murakami,1 Hideyuki Banno,1 Kazunori Nakajima,2† and Mitsuharu Hattori1† 1Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi 467-8603, Japan, and 2Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan During brain development, Reelin exerts a variety of effects in a context-dependent manner, whereas its underlying molecular mecha- nisms remain poorly understood. We previously showed that the C-terminal region (CTR) of Reelin is required for efficient induction of phosphorylation of Dab1, an essential adaptor protein for canonical Reelin signaling. However, the physiological significance of the Reelin CTR in vivo remains unexplored. To dissect out Reelin functions, we made a knock-in (KI) mouse in which the Reelin CTR is deleted. The amount of Dab1, an indication of canonical Reelin signaling strength, is increased in the KI mouse, indicating that the CTR is necessary for efficient induction of Dab1 phosphorylation in vivo. Formation of layer structures during embryonic development is normal in the KI mouse. Intriguingly, the marginal zone (MZ) of the cerebral cortex becomes narrower at postnatal stages because upper-layer neurons invade the MZ and their apical dendrites are misoriented and poorly branched. Furthermore, Reelin undergoes proteolytic cleavage by proprotein convertases at a site located 6 residues from the C terminus, and it was suggested that this cleavage abrogates the Reelin binding to the neuronal cell membrane.
    [Show full text]
  • Increased Blood-Reelin-Levels in First Episode Schizophrenia
    RESEARCH ARTICLE Increased Blood-Reelin-Levels in First Episode Schizophrenia Tobias Hornig*, Lukas Sturm, Bernd Fiebich, Ludger Tebartz van Elst Department of Psychiatry, Albert-Ludwigs-University, Hauptstr. 5, 79104 Freiburg, Germany * [email protected] Abstract Background Reelin is an extracellular glycoprotein involved in several functions of brain development, synaptogenesis and dendritic proliferation. Numerous studies found perturbation in the reelin system and altered serum reelin levels in neuropsychiatric patients using the western blot pro- cedure. In the international literature, this is the first study that made use of an enzyme-linked immunosorbent assay to analyze serum reelin protein concentration quantitatively. OPEN ACCESS Citation: Hornig T, Sturm L, Fiebich B, Tebartz van Rationale Elst L (2015) Increased Blood-Reelin-Levels in First In order to study possible alterations in reelin blood levels in schizophrenia, we analyzed Episode Schizophrenia. PLoS ONE 10(8): e0134671. this signal in schizophrenic patients with a first episode hallucinatory and paranoid syn- doi:10.1371/journal.pone.0134671 drome and control subjects in a pilot study design. Editor: James D. Clelland, The Nathan Kline Institute, UNITED STATES Results Received: November 18, 2014 We found increased blood reelin protein concentration in schizophrenic patients compared Accepted: July 13, 2015 to healthy controls. Published: August 25, 2015 Copyright: © 2015 Hornig et al. This is an open Discussion access article distributed under the terms of the Our findings point to a relevant role of reelin metabolism in the pathogenesis of schizophrenia. Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any Reelin could be a biomarker for the course of disease or psychopharmacological treatment.
    [Show full text]
  • Reelin Signals Through Apolipoprotein E Receptor 2 and Cdc42 to Increase Growth Cone Motility and Filopodia Formation
    The Journal of Neuroscience, November 3, 2010 • 30(44):14759–14772 • 14759 Cellular/Molecular Reelin Signals through Apolipoprotein E Receptor 2 and Cdc42 to Increase Growth Cone Motility and Filopodia Formation Jost Leemhuis,1,2 Elisabeth Bouche´,1,3 Michael Frotscher,1,4 Frank Henle,1,2 Lutz Hein,2 Joachim Herz,1,6 Dieter K. Meyer,1,2 Marina Pichler,1,2 Gu¨nter Roth,5 Carsten Schwan,1,2 and Hans H. Bock1,3 1Center for Neuroscience, 2Institute of Experimental and Clinical Pharmacology and Toxicology, 3Department of Medicine II, 4Institute of Anatomy and Cell Biology, and 5Department of Microsystems Engineering, Albert-Ludwigs-University, 79104 Freiburg, Germany, and 6Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9046 Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/ PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development.
    [Show full text]
  • Characterization of Neural Cells Derived from Reelin-Deficient Schizophrenic Patient Ips Cells
    University of Central Florida STARS Electronic Theses and Dissertations, 2004-2019 2018 Characterization of Neural Cells Derived from Reelin-deficient Schizophrenic Patient iPS Cells Nicole Roberts Part of the Biotechnology Commons Find similar works at: https://stars.library.ucf.edu/etd University of Central Florida Libraries http://library.ucf.edu This Masters Thesis (Open Access) is brought to you for free and open access by STARS. It has been accepted for inclusion in Electronic Theses and Dissertations, 2004-2019 by an authorized administrator of STARS. For more information, please contact [email protected]. STARS Citation Roberts, Nicole, "Characterization of Neural Cells Derived from Reelin-deficient Schizophrenic Patient iPS Cells" (2018). Electronic Theses and Dissertations, 2004-2019. 6196. https://stars.library.ucf.edu/etd/6196 CHARACTERIZATION OF NEURAL CELLS DERIVED FROM REELIN-DEFICIENT SCHIZOPHRENIC PATIENT IPS CELLS by NICOLE Y. ROBERTS B.S. Biology & Psychology, Florida State University, 2010 A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the Burnett School of Biomedical Science in the College of Medicine at the University of Central Florida Orlando, Florida Fall Term 2018 Major Professor: Kiminobu Sugaya ABSTRACT Reelin is a large, extracellular glycoprotein that binds to several membrane receptors on neural stem cells (HNSCs), neural progenitor cells (NPCs), and neuroblasts of mammals to direct their migration. Previously, our lab established the presence of Reelin increased migration of wild-type fetal-derived HNSC’s, both in vitro and in vivo. In addition, we demonstrated that Reelin protein treatment also increases the formation of radial glia via Notch-1 signaling, in vitro.
    [Show full text]
  • The Secreted Glycoprotein Reelin Suppresses the Proliferation and Regulates the Distribution of Oligodendrocyte Progenitor Cells in the Embryonic Neocortex
    The Journal of Neuroscience, September 30, 2020 • 40(40):7625–7636 • 7625 Cellular/Molecular The Secreted Glycoprotein Reelin Suppresses the Proliferation and Regulates the Distribution of Oligodendrocyte Progenitor Cells in the Embryonic Neocortex Himari Ogino,1 Tsuzumi Nakajima,1 Yuki Hirota,2 Kohki Toriuchi,3 Mineyoshi Aoyama,3 Kazunori Nakajima,2 and Mitsuharu Hattori1 1Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan, 2Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan, and 3Department of Pathobiology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan Oligodendrocyte (OL) progenitor cells (OPCs) are generated, proliferate, migrate, and differentiate in the developing brain. Although the development of OPCs is prerequisite for normal brain function, the molecular mechanisms regulating their de- velopment in the neocortex are not fully understood. Several molecules regulate the tangential distribution of OPCs in the developing neocortex, but the cue molecule(s) that regulate their radial distribution remains unknown. Here, we demonstrate that the secreted glycoprotein Reelin suppresses the proliferation of OPCs and acts as a repellent for their migration in vitro. These functions rely on the binding of Reelin to its receptors and on the signal transduction involving the intracellular pro- tein Dab1. In the late embryonic neocortex of mice with attenuated Reelin signaling [i.e., Reelin heterozygote-deficient,
    [Show full text]