期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 37, 页码 9558-9571出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0132-16.2016
关键词
adult neurogenesis; Alzheimer's disease; coxsakievirus and adenovirus receptor; inflammation; synapse
资金
- EC European Commission FP7 [226992, 286071]
- L'Agence Nationale de la Recherche ANR, E-Rare
- La Fondation de France
- L'Association de Recherche pour la Sclerose Laterale Amyotrophique
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.
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