RT Journal Article
T1 Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
A1 Gómez-Arboledas, Ángela
A1 Davila, Jose Carlos
A1 Sánchez-Mejías, Elisabeth
A1 Navarro, Victoria
A1 Núñez-Díaz, Cristina
A1 Sánchez-Varo, Raquel María
A1 Sanchez-Mico, Maria Virtudes
A1 Trujillo-Estrada, Laura Isabel
A1 Fernández-Valenzuela, Juan José
A1 Vizuete, Marisa
A1 Comella, Joan X.
A1 Galea, Elena
A1 Vitorica Ferrández, Javier
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, Enfermedad de
AB 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.
PB Wiley
YR 2018
FD 2018-03
LK https://hdl.handle.net/10630/29417
UL https://hdl.handle.net/10630/29417
LA spa
NO Gomez-Arboledas A, Davila JC, Sanchez-Mejias E, Navarro V, Nuñez-Diaz C, Sanchez-Varo R, Sanchez-Mico MV, Trujillo-Estrada L, Fernandez-Valenzuela JJ, Vizuete M, Comella JX, Galea E, Vitorica J, Gutierrez A. Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease. Glia. 2018 Mar;66(3):637-653. doi: 10.1002/glia.23270. Epub 2017 Nov 27. PMID: 29178139; PMCID: PMC5814816.
NO - Fundación La Marató-TV3: ref. 20141432 (para A. G.), ref. 20141431 (J. V.), ref. 20141433 (J. X. C.) y ref. 20141430 (E. G.).- Fondo de Investigación Sanitaria (FIS) del Instituto de Salud Carlos III (ISCiii) cofinanciado por fondos FEDER, los proyectos PI15/00796 (A. G.) y PI15/00957 (J. V.)- CIBERNED: PI2015-2/02 (A. G., J. V., y J. X. C.)- Junta de Andalucía, Proyecto de Excelencia ref. CTS-2035 (J. V. y A. G.).
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026