Neuronal Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes.
Neuron
; 108(5): 937-952.e7, 2020 12 09.
Article
en En
| MEDLINE
| ID: mdl-32979312
ABSTRACT
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 Aß, and for understanding how neuronal activity can modulate diurnal processes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
/
Ritmo Circadiano
/
Células Endoteliales
/
Relojes Circadianos
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2020
Tipo del documento:
Article