Open AccessBmal1 knockdown suppresses wake and increases immobility without altering orexin A, corticotrophin‐releasing hormone, or glutamate decarboxylase
Author(s) -
Akladious Afaf,
Azzam Sausan,
Hu Yufen,
Feng Pingfu
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12815
Subject(s) - endocrinology , medicine , orexin , orexin a , glutamate decarboxylase , wakefulness , gene knockdown , narcolepsy , sleep (system call) , lateral hypothalamus , chemistry , hypothalamus , neuropeptide , enzyme , neurology , electroencephalography , psychiatry , gene , computer science , operating system , biochemistry , receptor
Summary Objective To determine the effect of Bmal1 knockdown ( KD ) on sleep, activity, immobility, hypothalamic levels of orexin, corticotrophin‐releasing hormone ( CRH ), and GABA ergic glutamate decarboxylase ( GAD ). Methods We used Bmal1 si RNA , or control si RNA intracerebroventricular ( ICV ) injection to knock down Bmal1 in C57 BL /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 si RNA 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 si RNA also affected sleep associated with changes in orexin levels.