PMID- 29446232
OWN - NLM
STAT- MEDLINE
DCOM- 20190524
LR  - 20210109
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 24
IP  - 6
DP  - 2018 Jun
TI  - Bmal1 knockdown suppresses wake and increases immobility without altering orexin 
      A, corticotrophin-releasing hormone, or glutamate decarboxylase.
PG  - 549-563
LID - 10.1111/cns.12815 [doi]
AB  - OBJECTIVE: To determine the effect of Bmal1 knockdown (KD) on sleep, activity, 
      immobility, hypothalamic levels of orexin, corticotrophin-releasing hormone 
      (CRH), and GABAergic glutamate decarboxylase (GAD). METHODS: We used Bmal1 siRNA, 
      or control siRNA intracerebroventricular (ICV) injection to knock down Bmal1 in 
      C57BL/6 mice. Sleep polysomnography, wheel-running activity, and tail suspension 
      test were performed. Polysomnographic (PSG) recordings in both groups were 
      preceded by ICV injection made during both the light phase and the dark phase. We 
      also measured brain orexin A and CRH using an ELISA and measured GAD using 
      immunoblotting. RESULTS: Compared with control group, Bmal1 KD group had reduced 
      wheel activity and increased immobility. Compared with control, the Bmal1 KD 
      group had reduced wheel activity and increased immobility. During the first 
      24 hours after treatment, we observed that control siRNA induced a much greater 
      increase in sleep during the dark phase, which was associated with lower orexin 
      levels. However, beginning 24 hours after treatment, we observed an increase in 
      sleep and a decrease in time spent awake during the dark phase in the Bmal1 KD 
      group. These changes were not associated with changes in brain levels of orexin 
      A, CRH, or GAD. CONCLUSION: Bmal1 KD led to reduced activity, increased 
      immobility, and dramatic reduction in time spent awake as well as an increase in 
      sleep during the dark phase. Early after injection, there was a slight change in 
      sleep but brain levels of orexin, CRH, and GAD remain unchanged. Control siRNA 
      also affected sleep associated with changes in orexin levels.
CI  - Published 2018. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Akladious, Afaf
AU  - Akladious A
AD  - Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
FAU - Azzam, Sausan
AU  - Azzam S
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve 
      University, Cleveland, OH, USA.
FAU - Hu, Yufen
AU  - Hu Y
AD  - Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve 
      University, Cleveland, OH, USA.
FAU - Feng, Pingfu
AU  - Feng P
AUID- ORCID: 0000-0002-8267-5524
AD  - Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve 
      University, Cleveland, OH, USA.
LA  - eng
GR  - I01 BX001814/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180214
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (ARNTL Transcription Factors)
RN  - 0 (Orexins)
RN  - 0 (RNA, Small Interfering)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - ARNTL Transcription Factors/*deficiency/genetics
MH  - Animals
MH  - Corticotropin-Releasing Hormone/*metabolism
MH  - Disease Models, Animal
MH  - Electroencephalography
MH  - Electromyography
MH  - Gene Expression Regulation/genetics
MH  - Glutamate Decarboxylase/*metabolism
MH  - Hindlimb Suspension
MH  - Injections, Intraventricular
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Movement Disorders/*genetics/metabolism
MH  - Orexins/*metabolism
MH  - Polysomnography
MH  - RNA, Small Interfering/administration & dosage
MH  - Sleep Wake Disorders/*genetics
MH  - Wakefulness/genetics
PMC - PMC6490068
OTO - NOTNLM
OT  - Bmal1 knockdown
OT  - CRH
OT  - GAD
OT  - immobility
OT  - orexin
OT  - sleep
EDAT- 2018/02/16 06:00
MHDA- 2019/05/28 06:00
PMCR- 2018/02/14
CRDT- 2018/02/16 06:00
PHST- 2017/03/16 00:00 [received]
PHST- 2018/01/02 00:00 [revised]
PHST- 2018/01/10 00:00 [accepted]
PHST- 2018/02/16 06:00 [pubmed]
PHST- 2019/05/28 06:00 [medline]
PHST- 2018/02/16 06:00 [entrez]
PHST- 2018/02/14 00:00 [pmc-release]
AID - CNS12815 [pii]
AID - 10.1111/cns.12815 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2018 Jun;24(6):549-563. doi: 10.1111/cns.12815. Epub 2018 Feb 
      14.