Impaired Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex of Fmr1 Knock-Out Mice
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
RNA-Binding Protein Network Alteration Causes Aberrant Axon
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.26.268631; this version posted August 26, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 RNA-binding protein network alteration causes aberrant axon 2 branching and growth phenotypes in FUS ALS mutant motoneurons 3 4 Maria Giovanna Garone1, Nicol Birsa2,3, Maria Rosito4, Federico Salaris1,4, Michela Mochi1, Valeria 5 de Turris4, Remya R. Nair5, Thomas J. Cunningham5, Elizabeth M. C. Fisher2, Pietro Fratta2 and 6 Alessandro Rosa1,4,6,* 7 8 1. Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, P.le 9 A. Moro 5, 00185 Rome, Italy 10 2. UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, 11 UK 12 3. UK Dementia Research Institute, University College London, London, WC1E 6BT, UK 13 4. Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 14 Rome, Italy 15 5. MRC Harwell Institute, Oxfordshire, OX11 0RD, UK 16 6. Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of 17 Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Viale Regina Elena 18 291, 00161 Rome, Italy 19 20 * Corresponding author: [email protected]; Tel: +39-0649255218 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.26.268631; this version posted August 26, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Analysis of Proteins That Rapidly Change Upon Mechanistic
crossmark Research © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. This paper is available on line at http://www.mcponline.org Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC)*□S Farr Niere‡§¶ʈ§§, Sanjeev Namjoshi‡§ §§, Ehwang Song**, Geoffrey A. Dilly‡§¶, Grant Schoenhard‡‡, Boris V. Zemelman‡§¶, Yehia Mechref**, and Kimberly F. Raab-Graham‡§¶ʈ‡‡¶¶ Many biological processes involve the mechanistic/mam- ally alters the expression of proteins associated with malian target of rapamycin complex 1 (mTORC1). Thus, epilepsy, Alzheimer’s disease, and autism spectrum the challenge of deciphering mTORC1-mediated func- disorder—neurological disorders that exhibit elevated tions during normal and pathological states in the central mTORC1 activity. Through a protein–protein interaction nervous system is challenging. Because mTORC1 is at the network analysis, we have identified common proteins core of translation, we have investigated mTORC1 func- shared among these mTORC1-related diseases. One such tion in global and regional protein expression. Activation protein is Parkinson protein 7, which has been implicated of mTORC1 has been generally regarded to promote in Parkinson’s disease, yet not associated with epilepsy, translation. Few but recent works have shown that sup- Alzheimers disease, or autism spectrum disorder. To ver- pression of mTORC1 can also promote local protein syn- ify our finding, we provide evidence that the protein ex- thesis. Moreover, excessive mTORC1 activation during pression of Parkinson protein 7, including new protein diseased states represses basal and activity-induced pro- synthesis, is sensitive to mTORC1 inhibition. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Identification of a Mutation in Synapsin I, a Synaptic Vesicle Protein, in a Family with Epilepsy J Med Genet: First Published As on 1 March 2004
183 SHORT REPORT Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy J Med Genet: first published as on 1 March 2004. Downloaded from C C Garcia, H J Blair, M Seager, A Coulthard, S Tennant, M Buddles, A Curtis, J A Goodship ............................................................................................................................... J Med Genet 2004;41:183–187. doi: 10.1136/jmg.2003.013680 hippocampal bodies are moderately atrophic but without A four generation family is described in which some men of signal intensities. normal intelligence have epilepsy and others have various III-2 is a 64 year old man who has had a cerebrovascular combinations of epilepsy, learning difficulties, macrocephaly, accident but was previously of normal intelligence. He had and aggressive behaviour. As the phenotype in this family is tonic-clonic seizures until aged 7. His head circumference is distinct from other X linked recessive disorders linkage studies normal. were carried out. Linkage analysis was done using X III-3 is a 53 year old man with a full scale IQ that has been chromosome microsatellite polymorphisms to define the formally assessed as 72 (with the recognised error in such interval containing the causative gene. Genes from within assessments this places him within the borderline to mild the region were considered possible candidates and one of learning difficulties range). His head circumference is these, SYN1, was screened for mutations by direct DNA normal. As a teenager, he showed extreme physical aggres- sequencing of amplified products. Microsatellite analysis sion (he was held in a high security psychiatric hospital showed that the region between MAOB (Xp11.3) and between the ages of 11 and 18). -
Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering After Endocytosis
Neuron Article Increased Expression of a-Synuclein Reduces Neurotransmitter Release by Inhibiting Synaptic Vesicle Reclustering after Endocytosis Venu M. Nemani,1 Wei Lu,2 Victoria Berge,3 Ken Nakamura,1 Bibiana Onoa,1 Michael K. Lee,4 Farrukh A. Chaudhry,3 Roger A. Nicoll,2 and Robert H. Edwards1,* 1Departments of Neurology and Physiology, Graduate Program in Neuroscience 2Department of Cellular and Molecular Pharmacology University of California, San Francisco, San Francisco, CA 94158, USA 3The Biotechnology Centre of Oslo, Centre for Molecular Biology and Neuroscience, University of Oslo, Oslo, Norway 4Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA *Correspondence: [email protected] DOI 10.1016/j.neuron.2009.12.023 SUMMARY Parkinson’s disease (PD) and Lewy body dementia (LBD) (Spill- antini et al., 1998; Dickson, 2001). Point mutations in asyn are The protein a-synuclein accumulates in the brain of also linked to an autosomal-dominant form of PD (Polymeropou- patients with sporadic Parkinson’s disease (PD), los et al., 1997; Kru¨ ger et al., 1998; Zarranz et al., 2004). Taken and increased gene dosage causes a severe, domi- together, these observations suggest a causative role for asyn nantly inherited form of PD, but we know little about in sporadic as well as inherited PD and LBD. In addition, duplica- the effects of synuclein that precede degeneration. tion and triplication of the asyn gene suffice to cause a severe, a-Synuclein localizes to the nerve terminal, but the highly penetrant form of PD (Singleton et al., 2003; Chartier- Harlin et al., 2004), and polymorphisms in regulatory elements knockout has little if any effect on synaptic transmis- of the asyn gene predispose to PD (Maraganore et al., 2006), sion. -
A Novel Method of Neural Differentiation of PC12 Cells by Using Opti-MEM As a Basic Induction Medium
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 41: 195-201, 2018 A novel method of neural differentiation of PC12 cells by using Opti-MEM as a basic induction medium RENDONG HU1*, QIAOYU CAO2*, ZHONGQING SUN3, JINYING CHEN4, QING ZHENG2 and FEI XIAO1 1Department of Pharmacology, School of Medicine, Jinan University; 2College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632; 3Department of Anesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, SAR; 4Department of Ophthalmology, The First Clinical Medical College of Jinan University, Guangzhou, Guangdong 510632, P.R. China Received April 5, 2017; Accepted October 11, 2017 DOI: 10.3892/ijmm.2017.3195 Abstract. The PC12 cell line is a classical neuronal cell model Introduction due to its ability to acquire the sympathetic neurons features when deal with nerve growth factor (NGF). In the present study, The PC12 cell line is traceable to a pheochromocytoma from the authors used a variety of different methods to induce PC12 the rat adrenal medulla (1-4). When exposed to nerve growth cells, such as Opti-MEM medium containing different concen- factor (NGF), PC12 cells present an observable change in trations of fetal bovine serum (FBS) and horse serum compared sympathetic neuron phenotype and properties. Neural differ- with RPMI-1640 medium, and then observed the neurite length, entiation of PC12 has been widely used as a neuron cell model differentiation, adhesion, cell proliferation and action poten- in neuroscience, such as in the nerve injury-induced neuro- tial, as well as the protein levels of axonal growth-associated pathic pain model (5) and nitric oxide-induced neurotoxicity protein 43 (GAP-43) and synaptic protein synapsin-1, among model (6). -
DNA Methylation, Mechanisms of FMR1 Inactivation and Therapeutic Perspectives for Fragile X Syndrome
biomolecules Review DNA Methylation, Mechanisms of FMR1 Inactivation and Therapeutic Perspectives for Fragile X Syndrome Veronica Nobile 1, Cecilia Pucci 1, Pietro Chiurazzi 1,2 , Giovanni Neri 1,3 and Elisabetta Tabolacci 1,* 1 Sezione di Medicina Genomica, Dipartimento Scienze della Vita e Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; [email protected] (V.N.); [email protected] (C.P.); [email protected] (P.C.); [email protected] (G.N.) 2 Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Genetica Medica, 00168 Rome, Italy 3 Greenwood Genetic Center, JC Self Research Institute, Greenwood, SC 29646, USA * Correspondence: [email protected]; Tel.: +39-06-30154606 Abstract: Among the inherited causes of intellectual disability and autism, Fragile X syndrome (FXS) is the most frequent form, for which there is currently no cure. In most FXS patients, the FMR1 gene is epigenetically inactivated following the expansion over 200 triplets of a CGG repeat (FM: full mutation). FMR1 encodes the Fragile X Mental Retardation Protein (FMRP), which binds several mRNAs, mainly in the brain. When the FM becomes methylated at 10–12 weeks of gestation, the FMR1 gene is transcriptionally silent. The molecular mechanisms involved in the epigenetic silencing are not fully elucidated. Among FXS families, there is a rare occurrence of males carrying a FM, which remains active because it is not methylated, thus ensuring enough FMRPs to allow for an intellectual development within normal range. Which mechanisms are responsible for sparing these individuals from being affected by FXS? In order to answer this critical question, which may have possible implications for FXS therapy, several potential epigenetic mechanisms have been described. -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
Therapeutic Strategies in Fragile X Syndrome: Dysregulated Mglur Signaling and Beyond
Neuropsychopharmacology REVIEWS (2012) 37, 178–195 & 2012 American College of Neuropsychopharmacology All rights reserved 0893-133X/12 ............................................................................................................................................................... REVIEW 178 www.neuropsychopharmacology.org Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond 1 ,2 ,1,3 Christina Gross , Elizabeth M Berry-Kravis* and Gary J Bassell* 1 2 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA; Departments of Pediatrics, Neurology, 3 and Biochemistry, Rush University Medical Center, Chicago, IL, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. -
Role of Phosphodiesterases in the Pathophysiology of Neurodevelopmental Disorders
Molecular Psychiatry https://doi.org/10.1038/s41380-020-00997-9 REVIEW ARTICLE Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders 1 2 Sébastien Delhaye ● Barbara Bardoni Received: 4 July 2020 / Revised: 3 December 2020 / Accepted: 9 December 2020 © The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature 2021. This article is published with open access Abstract Phosphodiesterases (PDEs) are enzymes involved in the homeostasis of both cAMP and cGMP. They are members of a family of proteins that includes 11 subfamilies with different substrate specificities. Their main function is to catalyze the hydrolysis of cAMP, cGMP, or both. cAMP and cGMP are two key second messengers that modulate a wide array of intracellular processes and neurobehavioral functions, including memory and cognition. Even if these enzymes are present in all tissues, we focused on those PDEs that are expressed in the brain. We took into consideration genetic variants in patients affected by neurodevelopmental disorders, phenotypes of animal models, and pharmacological effects of PDE inhibitors, a class of drugs in rapid evolution and increasing application to brain disorders. Collectively, these data indicate the potential 1234567890();,: 1234567890();,: of PDE modulators to treat neurodevelopmental diseases characterized by learning and memory impairment, alteration of behaviors associated with depression, and deficits in social interaction. Indeed, clinical trials are in progress to treat patients with Alzheimer’s disease, schizophrenia, depression, and autism spectrum disorders. Among the most recent results, the application of some PDE inhibitors (PDE2A, PDE3, PDE4/4D, and PDE10A) to treat neurodevelopmental diseases, including autism spectrum disorders and intellectual disability, is a significant advance, since no specific therapies are available for these disorders that have a large prevalence. -
Selective Lowering of Synapsins Induced by Oligomeric Α-Synuclein Exacerbates Memory Deficits
Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits Megan E. Larsona,b,c,1, Susan J. Greimela,b,c,1, Fatou Amara,b,c, Michael LaCroixa,b,c, Gabriel Boylea,b,c, Mathew A. Shermana,b,c, Hallie Schleya,b,c, Camille Miela,b,c, Julie A. Schneiderd, Rakez Kayede, Fabio Benfenatif,g, Michael K. Leea,c, David A. Bennettd, and Sylvain E. Lesnéa,b,c,2 aDepartment of Neuroscience, University of Minnesota, Minneapolis, MN 55414; bN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55414; cInstitute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55414; dRush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL 60612; eDepartment of Neurology, University of Texas Medical Branch, Galveston, TX 77555; fCenter for Synaptic Neuroscience, Istituto Italiano di Tecnologia, 16132 Genoa, Italy; and gDepartment of Experimental Medicine, University of Genova, 16132 Genoa, Italy Edited by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved April 24, 2017 (received for review April 4, 2017) Mounting evidence indicates that soluble oligomeric forms of a reduction in the synaptic vesicle recycling pool, and a selective amyloid proteins linked to neurodegenerative disorders, such as lowering of complexins and synapsins (8). Moreover, large mul- amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major del- timeric assemblies of recombinant αSyn were recently shown to eterious species for neuronal function in these diseases. Here, we inhibit exocytosis by preferentially binding to synaptobrevin, found an abnormal accumulation of oligomeric αSyn species in AD thereby preventing normal SNARE-mediated vesicle docking (9). -
Cardiac Arrhythmia After Myocardial Infarction
CARDIAC ARRHYTHMIA AFTER MYOCARDIAL INFARCTION: INSIGHTS FROM A DYNAMIC CANINE VENTRICULAR MYOCYTE MODEL by Thomas J. Hund Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Advisor: Dr. Yoram Rudy Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May 2004 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the dissertation of ______________________________________________________ candidate for the Ph.D. degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. For Keila iii TABLE OF CONTENTS List of Tables ...................................................................................................................... 3 List of Figures..................................................................................................................... 4 Acknowledgments............................................................................................................... 6 List of Abbreviations .......................................................................................................... 7 Glossary .............................................................................................................................