Document Detail


Knockdown of orexin type 2 receptor in the lateral pontomesencephalic tegmentum of rats increases REM sleep.
MedLine Citation:
PMID:  23282008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dysfunction of the orexin/hypocretin neurotransmitter system causes the sleep disorder narcolepsy, characterized by intrusion of rapid eye movement (REM) sleep-like events into normal wakefulness. The sites where orexins act to suppress REM sleep are incompletely understood. Previous studies suggested that the lateral pontomesencephalic tegmentum (lPMT) contains an important REM sleep inhibitory area, and proposed that orexins inhibit REM sleep via orexin type 2 receptors (OxR2) in this region. However, this hypothesis has heretofore not been tested. We thus performed bilateral injection of small interfering RNAs (siRNAs) targeting Ox2R into the lPMT on two consecutive days. This led to a approximately 30% increase of time spent in REM sleep in both the dark and light periods for the first 2 days after injection, with a return to baseline over the next two post-injection days. This increase was mainly due to longer (> 120 s) REM episodes. Cataplexy-like episodes were not observed. The percentage of time spent in wakefulness and non-(N)REM sleep, as well as the power spectral profile of NREM and REM sleep, were unaffected. Control animals injected with scrambled siRNA had no sleep changes post-injection. Quantification of the knockdown revealed that unilateral microinjection of siRNAs targeting OxR2 into the lPMT induced a approximately 40% reduction of OxR2 mRNA 2 days following the injections when compared with the contralateral side receiving control (scrambled) siRNA. Orexin type 1 receptor mRNA level was unaffected. Our results indicate that removal of OxR2 neurotransmission in the lPMT enhances REM sleep by increasing the duration of REM episodes.
Authors:
Lichao Chen; James T McKenna; Yunren Bolortuya; Ritchie E Brown; Robert W McCarley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-03
Journal Detail:
Title:  The European journal of neuroscience     Volume:  37     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-19     Completed Date:  2013-08-29     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  957-63     Citation Subset:  IM    
Copyright Information:
Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Silencing
Male
Orexin Receptors
Photoperiod
RNA, Messenger / metabolism
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled / genetics,  metabolism*
Receptors, Neuropeptide / genetics,  metabolism*
Sleep, REM / genetics*
Tegmentum Mesencephali / metabolism,  physiology*
Transcription, Genetic
Wakefulness
Grant Support
ID/Acronym/Agency:
P01 HL095491/HL/NHLBI NIH HHS; R01 MH039683/MH/NIMH NIH HHS; R01 MH39683/MH/NIMH NIH HHS; R21 MH094803/MH/NIMH NIH HHS; R21 MH094803/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Orexin Receptors; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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