PMID- 33679370
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210310
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 13
DP  - 2021
TI  - Extracellular Vesicles From 3xTg-AD Mouse and Alzheimer's Disease Patient 
      Astrocytes Impair Neuroglial and Vascular Components.
PG  - 593927
LID - 10.3389/fnagi.2021.593927 [doi]
LID - 593927
AB  - Astrocytes are specialized glial cells that are essential components of the 
      neurovascular unit (NVU) and are involved in neurodevelopment, brain maintenance 
      and repair, and neurodegeneration. Astrocytes mediate these processes by 
      releasing cellular mediators such as extracellular vesicles (EVs). EVs are 
      vehicles of cell-cell communication and have been proposed as mediators of damage 
      in AD. However, the transcellular mechanism by which Alzheimer disease (AD) 
      astrocytes impair the function of NVU components is poorly understood. Therefore, 
      we evaluated the effects of adult PS1-KI and 3xTg-AD astrocyte conditioned media 
      (CM) and EVs on NVU components (neuroglia and endothelium) in vitro. 
      Additionally, SAD and FAD astrocyte-derived EVs (A-EVs) were characterized, and 
      we evaluated their effects on NVU in cocultured cells in vitro and on 
      intrahippocampal CA1 cells in vivo. Surprisingly, cultured 3xTg-AD astrocytes 
      showed increased glial fibrillary acidic protein (GFAP) reactivity compared to 
      PS1-KI astrocytes, which denotes astrocytic hyperreactivity. CM from adult mice 
      3xTg-AD astrocytes increased cell-cell gaps between endothelial cells, 
      filopodia-like dendritic protrusions in neurons and neuronal and endothelial cell 
      death. 3xTg-AD A-EVs induced neurotoxicity and increased astrocyte GFAP 
      reactivity. Cultured human postmortem astrocytes from AD patients also increased 
      GFAP reactivity and EVs release. No differences in the size or number of A-EVs 
      were detected between AD and control samples; however, both SAD and FAD A-EVs 
      showed increased expression of the surface marker aquaporin 4. A-EVs induced 
      cytotoxicity and astrocyte hyperactivation: specifically, FAD A-EVs induced 
      neuroglial cytotoxicity and increased gaps between the endothelium, while SAD 
      A-EVs mainly altered the endothelium. Similarly, both AD A-EVs increased 
      astrocyte GS reactivity and vascular deterioration in vivo. We associated this 
      finding with perivascular reactive astrocytes and vascular deterioration in the 
      human AD brain. In summary, these results suggest that AD A-EVs impair neuroglial 
      and vascular components.
CI  - Copyright (c) 2021 Gonzalez-Molina, Villar-Vesga, Henao-Restrepo, Villegas, Lopera, 
      Cardona-Gomez and Posada-Duque.
FAU - Gonzalez-Molina, Luis Alfonso
AU  - Gonzalez-Molina LA
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
AD  - Facultad de Ciencias Exactas y Naturales, Instituto de Biologia, Universidad de 
      Antioquia, Medellin, Colombia.
FAU - Villar-Vesga, Juan
AU  - Villar-Vesga J
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
AD  - Facultad de Ciencias Exactas y Naturales, Instituto de Biologia, Universidad de 
      Antioquia, Medellin, Colombia.
FAU - Henao-Restrepo, Julian
AU  - Henao-Restrepo J
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
AD  - Facultad de Ciencias Exactas y Naturales, Instituto de Biologia, Universidad de 
      Antioquia, Medellin, Colombia.
FAU - Villegas, Andres
AU  - Villegas A
AD  - Neurobank, Neuroscience Group of Antioquia, Faculty of Medicine, SIU, University 
      of Antioquia, Medellin, Colombia.
FAU - Lopera, Francisco
AU  - Lopera F
AD  - Neurobank, Neuroscience Group of Antioquia, Faculty of Medicine, SIU, University 
      of Antioquia, Medellin, Colombia.
FAU - Cardona-Gomez, Gloria Patricia
AU  - Cardona-Gomez GP
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
FAU - Posada-Duque, Rafael
AU  - Posada-Duque R
AD  - Area de Neurobiologia Celular y Molecular, Grupo de Neurociencias de Antioquia, 
      Universidad de Antioquia, Medellin, Colombia.
AD  - Facultad de Ciencias Exactas y Naturales, Instituto de Biologia, Universidad de 
      Antioquia, Medellin, Colombia.
LA  - eng
PT  - Journal Article
DEP - 20210219
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC7933224
OTO - NOTNLM
OT  - 3xTg-AD mice
OT  - astrocytes
OT  - endothelial disruption
OT  - extracellular vesicles
OT  - familiar Alzheimer's disease
OT  - human astrocytes
OT  - sporadic Alzheimer disease
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/03/09 06:00
MHDA- 2021/03/09 06:01
PMCR- 2021/01/01
CRDT- 2021/03/08 05:49
PHST- 2020/08/11 00:00 [received]
PHST- 2021/01/21 00:00 [accepted]
PHST- 2021/03/08 05:49 [entrez]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2021/03/09 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2021.593927 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2021 Feb 19;13:593927. doi: 10.3389/fnagi.2021.593927. 
      eCollection 2021.