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TitleCoxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity.
Publication TypeJournal Article
Year of Publication2016
AuthorsZussy, Charleine, Fabien Loustalot, Felix Junyent, Fabrizio Gardoni, Cyril Bories, Jorge Valero, Michel G. Desarménien, Florence Bernex, Daniel Henaff, Neus Bayo-Puxan, Jin-Wen Chen, Nicolas Lonjon, Yves De Koninck, João O. Malva, Jeffrey M. Bergelson, Monica di Luca, Giampietro Schiavo, Sara Salinas, and Eric J. Kremer
JournalJ Neurosci
Volume36
Issue37
Pagination9558-71
Date Published2016 Sep 14
ISSN1529-2401
Abstract

UNLABELLED: 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.

SIGNIFICANCE STATEMENT: 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.

DOI10.1523/JNEUROSCI.0132-16.2016
Alternate JournalJ. Neurosci.
PubMed ID27629708