title: Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity.
abstract: Although we are beginning to understand the late stage of neurodegenerative diseases, the molecular defects associated with the initiation of impaired cognition are poorly characterized. Here, we demonstrate that in the adult brain, the coxsackievirus and adenovirus receptor (CAR) is located on neuron projections, at the presynapse in mature neurons, and on the soma of immature neurons in the hippocampus. In a proinflammatory or diseased environment, CAR is lost from immature neurons in the hippocampus. Strikingly, in hippocampi of patients at early stages of late-onset Alzheimer's disease (AD), CAR levels are significantly reduced. Similarly, in triple-transgenic AD mice, CAR levels in hippocampi are low and further reduced after systemic inflammation. Genetic deletion of CAR from the mouse brain triggers deficits in adult neurogenesis and synapse homeostasis that lead to impaired hippocampal plasticity and cognitive deficits. We propose that post-translational CAR loss of function contributes to cognitive defects in healthy and diseased-primed brains.
  
  
  
  This study addressed the role of the coxsackievirus and adenovirus receptor (CAR), a single-pass cell adhesion molecule, in the adult brain. Our results demonstrate that CAR is expressed by mature neurons throughout the brain. In addition, we propose divergent roles for CAR in immature neurons, during neurogenesis, and at the mature synapse. Notably, CAR loss of function also affects hippocampal plasticity.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
authors.forename: Charleine
authors.initials: C
authors.lastname: Zussy
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Loustalot
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
authors.forename: Felix
authors.initials: F
authors.lastname: Junyent
authors.affiliation: Università degli Studi di Milano, Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, 20122 Milan, Italy.
authors.forename: Fabrizio
authors.identifier: 0000-0003-4598-5563
authors.initials: F
authors.lastname: Gardoni
authors.affiliation: Mental Health Institute of Quebec and Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec City, G1V 0A6 Quebec, Canada.
authors.forename: Cyril
authors.initials: C
authors.lastname: Bories
authors.affiliation: Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Jorge
authors.identifier: 0000-0001-6072-3313
authors.initials: J
authors.lastname: Valero
authors.affiliation: Université de Montpellier, 34000 Montpellier, France, Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Inserm, 34394 Montpellier, France.
authors.forename: Michel G
authors.identifier: 0000-0003-0902-0043
authors.initials: MG
authors.lastname: Desarménien
authors.affiliation: Institut Régional du Cancer Montpellier, Inserm, 34090 Montpellier, France.
authors.forename: Florence
authors.identifier: 0000-0003-0366-4315
authors.initials: F
authors.lastname: Bernex
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
authors.forename: Daniel
authors.identifier: 0000-0003-2219-5083
authors.initials: D
authors.lastname: Henaff
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
authors.forename: Neus
authors.identifier: 0000-0001-9909-1499
authors.initials: N
authors.lastname: Bayo-Puxan
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Jin-Wen
authors.identifier: 0000-0002-4997-1647
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Département de Neurochirurgie, Hôpital Gui de Chauliac, 34000 Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lonjon
authors.affiliation: Mental Health Institute of Quebec and Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec City, G1V 0A6 Quebec, Canada.
authors.forename: Yves
authors.identifier: 0000-0002-5779-9330
authors.initials: Y
authors.lastname: de Koninck
authors.affiliation: Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: João O
authors.initials: JO
authors.lastname: Malva
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bergelson
authors.affiliation: Università degli Studi di Milano, Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, 20122 Milan, Italy.
authors.forename: Monica
authors.identifier: 0000-0003-2298-615X
authors.initials: M
authors.lastname: di Luca
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom, and.
authors.forename: Giampietro
authors.identifier: 0000-0002-4319-8745
authors.initials: G
authors.lastname: Schiavo
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France, sara.salinas@inserm.fr eric.kremer@igmm.cnrs.fr.
authors.forename: Sara
authors.identifier: 0000-0003-4492-2093
authors.initials: S
authors.lastname: Salinas
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France, sara.salinas@inserm.fr eric.kremer@igmm.cnrs.fr.
authors.forename: Eric J
authors.identifier: 0000-0001-6114-7530
authors.initials: EJ
authors.lastname: Kremer
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000209:etiology; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000172:deficiency* / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D013569:Synapses / Q000378:metabolism*
chemical_list: C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D016207:Cytokines; D064231:Nestin
keywords: Alzheimer's disease; adult neurogenesis; coxsakievirus and adenovirus receptor; inflammation; synapse