Abstract
HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aβ pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Aβ cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred Aβ to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent Aβ into the internal carotid artery of mice resulted in Aβ fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying Aβ can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying Aβ; a process that may increase Aβ exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12-22 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Neuroscience |
| Volume | 79 |
| DOIs | |
| State | Published - Mar 1 2017 |
Fingerprint
Keywords
- Amyloid beta
- Blood-brain barrier
- Extracellular vesicles
- HIV-1
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology
Cite this
Extracellular vesicles of the blood-brain barrier : Role in the HIV-1 associated amyloid beta pathology. / Andras, Ibolya Edit; Leda, Ana; Contreras, Marta Garcia; Bertrand, Luc; Park, Minseon; Skowronska, Marta; Toborek, Michal J.
In: Molecular and Cellular Neuroscience, Vol. 79, 01.03.2017, p. 12-22.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extracellular vesicles of the blood-brain barrier
T2 - Role in the HIV-1 associated amyloid beta pathology
AU - Andras, Ibolya Edit
AU - Leda, Ana
AU - Contreras, Marta Garcia
AU - Bertrand, Luc
AU - Park, Minseon
AU - Skowronska, Marta
AU - Toborek, Michal J
PY - 2017/3/1
Y1 - 2017/3/1
N2 - HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aβ pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Aβ cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred Aβ to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent Aβ into the internal carotid artery of mice resulted in Aβ fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying Aβ can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying Aβ; a process that may increase Aβ exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.
AB - HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced Aβ pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their Aβ cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred Aβ to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent Aβ into the internal carotid artery of mice resulted in Aβ fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying Aβ can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying Aβ; a process that may increase Aβ exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.
KW - Amyloid beta
KW - Blood-brain barrier
KW - Extracellular vesicles
KW - HIV-1
UR - http://www.scopus.com/inward/record.url?scp=85008311444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008311444&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2016.12.006
DO - 10.1016/j.mcn.2016.12.006
M3 - Article
C2 - 28040512
AN - SCOPUS:85008311444
VL - 79
SP - 12
EP - 22
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
SN - 1044-7431
ER -