Abstract
Circadian rhythm disturbances are well established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, and Bmal1 deficiency in male Bmal1nestin +/+ mice induced marked astroglial activation without affecting the number of astrocytes in the brain and spinal cord. Bmal1 deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss of pericyte coverage of blood vessels in the brain. Using Nestin-green fluorescent protein(GFP) transgenic mice, we determined that pericytes are Nestin-GFP+ in the adult brain. Bmal1 deletion caused Nestin-GFP+ pericyte dysfunction, including the downregulation of platelet-derived growth factor receptor β (PDGFRβ), a protein necessary for maintaining BBB integrity. Knockdown of Bmal1 downregulated PDGFRβ transcription in the brain pericyte cell line. Thus, the circadian clock component Bmal1 maintains BBB integrity via regulating pericytes.
| Original language | English |
|---|---|
| Pages (from-to) | 10052-10062 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 37 |
| Issue number | 42 |
| DOIs | |
| Publication status | Published - Oct 18 2017 |
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Keywords
- Blood-brain barrier
- Clock gene
- Pericyte
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Disruption of Bmal1 impairs blood-brain barrier integrity via pericyte dysfunction. / Nakazato, Ryota; Kawabe, Kenji; Yamada, Daisuke; Ikeno, Shinsuke; Mieda, Michihiro; Shimba, Shigeki; Hinoi, Eiichi; Yoneda, Yukio; Takarada, Takeshi.
In: Journal of Neuroscience, Vol. 37, No. 42, 18.10.2017, p. 10052-10062.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disruption of Bmal1 impairs blood-brain barrier integrity via pericyte dysfunction
AU - Nakazato, Ryota
AU - Kawabe, Kenji
AU - Yamada, Daisuke
AU - Ikeno, Shinsuke
AU - Mieda, Michihiro
AU - Shimba, Shigeki
AU - Hinoi, Eiichi
AU - Yoneda, Yukio
AU - Takarada, Takeshi
PY - 2017/10/18
Y1 - 2017/10/18
N2 - Circadian rhythm disturbances are well established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, and Bmal1 deficiency in male Bmal1nestin +/+ mice induced marked astroglial activation without affecting the number of astrocytes in the brain and spinal cord. Bmal1 deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss of pericyte coverage of blood vessels in the brain. Using Nestin-green fluorescent protein(GFP) transgenic mice, we determined that pericytes are Nestin-GFP+ in the adult brain. Bmal1 deletion caused Nestin-GFP+ pericyte dysfunction, including the downregulation of platelet-derived growth factor receptor β (PDGFRβ), a protein necessary for maintaining BBB integrity. Knockdown of Bmal1 downregulated PDGFRβ transcription in the brain pericyte cell line. Thus, the circadian clock component Bmal1 maintains BBB integrity via regulating pericytes.
AB - Circadian rhythm disturbances are well established in neurological diseases. However, how these disruptions cause homeostatic imbalances remains poorly understood. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) is a major circadian clock transcriptional activator, and Bmal1 deficiency in male Bmal1nestin +/+ mice induced marked astroglial activation without affecting the number of astrocytes in the brain and spinal cord. Bmal1 deletion caused blood-brain barrier (BBB) hyperpermeability with an age-dependent loss of pericyte coverage of blood vessels in the brain. Using Nestin-green fluorescent protein(GFP) transgenic mice, we determined that pericytes are Nestin-GFP+ in the adult brain. Bmal1 deletion caused Nestin-GFP+ pericyte dysfunction, including the downregulation of platelet-derived growth factor receptor β (PDGFRβ), a protein necessary for maintaining BBB integrity. Knockdown of Bmal1 downregulated PDGFRβ transcription in the brain pericyte cell line. Thus, the circadian clock component Bmal1 maintains BBB integrity via regulating pericytes.
KW - Blood-brain barrier
KW - Clock gene
KW - Pericyte
UR - http://www.scopus.com/inward/record.url?scp=85031901466&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031901466&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3639-16.2017
DO - 10.1523/JNEUROSCI.3639-16.2017
M3 - Article
C2 - 28912161
AN - SCOPUS:85031901466
VL - 37
SP - 10052
EP - 10062
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 42
ER -