Soluble Tau has devastating effects on the structural plasticity of hippocampal granule neurons
| Autor: | Marta Bolós, Juan Ramón Perea, Julia Terreros-Roncal, Jesús Avila, María Llorens-Martín, Jerónimo Jurado-Arjona, Noemí Pallas-Bazarra |
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| Přispěvatelé: | Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Ministerio de Economía y Competitividad (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dendritic spine Efferent tau Proteins Hippocampal formation Hippocampus Synaptic vesicle Article lcsh:RC321-571 Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine In vivo Neuroplasticity Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Neurons Neuronal Plasticity Chemistry Granule (cell biology) Psychiatry and Mental health 030104 developmental biology Ultrastructure Synaptic Vesicles Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 7, Iss 12, Pp 1-16 (2017) Digital.CSIC. Repositorio Institucional del CSIC instname Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Tau is a neuronal microtubule-associated protein with countless physiological functions. Although the detrimental effects of insoluble aggregated Tau have been widely studied, recent evidence supports the notion that soluble Tau (composed mostly of monomers and dimers) is also toxic for neurons. Here we evaluated the long-term impact of a single stereotaxic injection of human soluble Tau on hippocampal granule neurons in mice. At the ultrastructural level, soluble Tau reduced the number of afferent synapses and caused a dramatic depletion of synaptic vesicles both in afferent and efferent synapses. Furthermore, the use of an RFP-expressing retrovirus revealed that soluble Tau altered the morphology of newborn granule neurons and reduced their afferent (dendritic spines) and efferent (mossy fiber terminals) connectivity. Finally, soluble Tau caused specific impairment of behavioral pattern separation capacity. Our results thus demonstrate for the first time that soluble Tau causes long-term detrimental effects on the morphology and connectivity of newborn granule neurons and that these effects correlate with impaired behavioral pattern separation skills. These data might be relevant for the field of neurodegenerative disorders, since they contribute to reinforcing the pathological roles played by distinct Tau species in vivo. Spanish Ministry of Economy and Competitiveness (SAF-2014-53040-P (to J.Á.) and RYC-2015-17189 (to M.LL.-M.)); the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain) |
| Databáze: | OpenAIRE |
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