Neuronal Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes
Copyright © 2020 Elsevier Inc. All rights reserved..
The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Aβ, and for understanding how neuronal activity can modulate diurnal processes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:108 |
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| Enthalten in: |
Neuron - 108(2020), 5 vom: 09. Dez., Seite 937-952.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pulido, Robert S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.01.2021 Date Revised 21.01.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuron.2020.09.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315500387 |
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| 500 | |a Date Revised 21.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Aβ, and for understanding how neuronal activity can modulate diurnal processes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Blood-Brain Barrier | |
| 650 | 4 | |a Cerebrovascular Function | |
| 650 | 4 | |a Circadian Rhythms | |
| 650 | 4 | |a Efflux transport | |
| 650 | 4 | |a Neuronal Activity | |
| 650 | 4 | |a Neurovascular Signaling | |
| 650 | 4 | |a P-glycoprotein | |
| 650 | 4 | |a Transcriptomics | |
| 650 | 7 | |a Designer Drugs |2 NLM | |
| 700 | 1 | |a Munji, Roeben N |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Tamara C |e verfasserin |4 aut | |
| 700 | 1 | |a Quirk, Clare R |e verfasserin |4 aut | |
| 700 | 1 | |a Weiner, Geoffrey A |e verfasserin |4 aut | |
| 700 | 1 | |a Weger, Benjamin D |e verfasserin |4 aut | |
| 700 | 1 | |a Rossi, Meghan J |e verfasserin |4 aut | |
| 700 | 1 | |a Elmsaouri, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Malfavon, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Profaci, Caterina P |e verfasserin |4 aut | |
| 700 | 1 | |a Blanchette, Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Tongcheng |e verfasserin |4 aut | |
| 700 | 1 | |a Foreman, Koji L |e verfasserin |4 aut | |
| 700 | 1 | |a Shusta, Eric V |e verfasserin |4 aut | |
| 700 | 1 | |a Gorman, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Gachon, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Leutgeb, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Daneman, Richard |e verfasserin |4 aut | |
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