Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
Gomez-Arboledas, Angela (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Davila, Jose C. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Sanchez-Mejias, Elisabeth (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Navarro, Victoria (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Nuñez-Diaz, Cristina (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Sanchez-Varo, Raquel (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Sanchez-Mico, Maria Virtudes (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Trujillo-Estrada, Laura (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Fernandez-Valenzuela, Juan Jose (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Vizuete, Marisa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Comella i Carnicé, Joan Xavier 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Galea, Elena (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Vitorica, Javier (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Gutiérrez Pérez, Antonia (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)

Fecha:	2017
Resumen:	Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque-associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the accumulation of dystrophic neurites during disease course, suggests that the efficiency of the astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer's patients by confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytes might contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impaired neural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limiting the amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytes may represent a potential therapy in Alzheimer's disease.
Ayudas:	Instituto de Salud Carlos III PI15-00796 Instituto de Salud Carlos III PI15-00957
Nota:	Altres ajuts: This work was supported by La Marató-TV3 Foundation grants 20141432 (to A. G.), 20141431 (to J. V.), 20141433 (to J. X. C.) and 20141430 (to E. G.); by CIBERNED PI2015-2/02 (to A. G., J. V., and J. X. C.); and by Junta de Andalucia, Proyecto de Excelencia (CTS-2035) (to J. V. and A. G.). We thank to Rocio Romero Pareja from FESEM-FIB Unit (Bioinnovation Building, University of Malaga, Spain) and Mercedes Aneiros Ferrer for their expert technical assistance.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; Neurodegeneration ; Neuropathology ; Reactive astrocyte ; Synaptopathy
Publicado en:	GLIA, Vol. 66 (november 2017) , p. 637-653, ISSN 1098-1136

DOI: 10.1002/glia.23270
PMID: 29178139

17 p, 3.6 MB

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