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J Neurosci. 2016 Sep 14;36(37):9558-71. doi: 10.1523/JNEUROSCI.0132-16.2016.

Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity.

Author information

1
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique 5535, 34293 Montpellier, France, Université de Montpellier, 34000 Montpellier, France.
2
Università degli Studi di Milano, Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, 20122 Milan, Italy.
3
Mental Health Institute of Quebec and Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec City, G1V 0A6 Quebec, Canada.
4
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
5
Université de Montpellier, 34000 Montpellier, France, Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique, Inserm, 34394 Montpellier, France.
6
Institut Régional du Cancer Montpellier, Inserm, 34090 Montpellier, France.
7
Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
8
Département de Neurochirurgie, Hôpital Gui de Chauliac, 34000 Montpellier, France.
9
Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom, and.
10
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.

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.

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.

KEYWORDS:

Alzheimer's disease; adult neurogenesis; coxsakievirus and adenovirus receptor; inflammation; synapse

PMID:
27629708
DOI:
10.1523/JNEUROSCI.0132-16.2016
[Indexed for MEDLINE]
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