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


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.

SUBMITTER: Zussy C 

PROVIDER: S-EPMC6601941 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Zussy Charleine C   Loustalot Fabien F   Junyent Felix F   Gardoni Fabrizio F   Bories Cyril C   Valero Jorge J   Desarménien Michel G MG   Bernex Florence F   Henaff Daniel D   Bayo-Puxan Neus N   Chen Jin-Wen JW   Lonjon Nicolas N   de Koninck Yves Y   Malva João O JO   Bergelson Jeffrey M JM   di Luca Monica M   Schiavo Giampietro G   Salinas Sara S   Kremer Eric J EJ  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20160901 37


<h4>Unlabelled</h4>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  ...[more]

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