Evidence map›Paper›PMID 21089218›Full record

ArticleThe European journal of neuroscience2010

Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep during the dark period.

Lichao Chen, James T McKenna, Yunren Bolortuya, Stuart Winston, Mahesh M Thakkar, Radhika Basheer, Ritchie E Brown, Robert W McCarley

Open access · greenAbstract read
In one paragraph

Article in The European journal of neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Article
  10. Review
  11. Article
  12. Animal models of sleep disorders.Comparative medicine · 2013
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Mechanism for Hypocretin-mediated sleep-to-wake transitions.Proceedings of the National Academy of Sciences of the United States of America · 2012
    Article
  18. Control of sleep and wakefulness.Physiological reviews · 2012
    Review
  19. Article
  20. Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus.American journal of physiology. Regulatory, integrative and comparative physiology · 2011
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Lichao ChenResearch Service, VA Boston Healthcare System, and Department of Psychiatry, Harvard Medical School, Brockton, MA 02301,USA. lichao_chen@hms.harvard.edu
James T McKenna
Yunren Bolortuya
Stuart Winston
Mahesh M Thakkar
Radhika Basheer
Ritchie E Brown
Robert W McCarley
VA Boston Healthcare System · USHarvard University · USUniversity of Missouri · US

Funding

THE SYNAPTIC BASIS OF SLEEP CYCLE CONTROLR01MH039683 · NIMH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BROWN, RITCHIE EDWARD · 1985 to 2017
$3.8M
OREXIN AND THE CONTROL OF SLEEP AND WAKEFULNESSR01MH062522 · NIMH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MC CARLEY, ROBERT W. · 2001 to 2005
$1.1M
ELECTROPHYSIOLOGY &PHARMACOLOGY OF SLEEP-WAKINGK01MH001798 · NIMH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI THAKKAR, MAHESH M · 2000 to 2004
$599k
Orexins in Rapid Eye Movement Sleep Control.R03NS059831 · NINDS · UNIVERSITY OF MISSOURI-COLUMBIA · PI THAKKAR, MAHESH M · 2008 to 2009
$122k
Sleep Spindles: Role of Thalamic Reticular Nucleus and Parvalbumin GABA NeuronsI01BX001356 · VA · VA BOSTON HEALTH CARE SYSTEM · PI BROWN, RITCHIE EDWARD · 2012 to 2020
–
BLRD VA I01 BX001356NIMH NIH HHS K01 MH001798NIMH NIH HHS R01 MH039683NIMH NIH HHS R01 MH062522NINDS NIH HHS NS059831NINDS NIH HHS R03 NS059831PHS HHS 01798PHS HHS 062522PHS HHS 39683
6 · The paper itself

Abstract

The locus coeruleus (LC) regulates sleep/wakefulness and is densely innervated by orexinergic neurons in the lateral hypothalamus. Here we used small interfering RNAs (siRNAs) to test the role of LC orexin type 1 receptor (OxR1) in sleep–wake control. In sleep studies, bilateral OxR1 siRNA injections led to an increase of time spent in rapid eye movement (REM) sleep, which was selective for the dark (active) period, peaked at approximately 30% of control during the second dark period after injection and then disappeared after 4 days. Cataplexy-like episodes were not observed. The percentage time spent in wakefulness and non-REM (NREM) sleep and the power spectral profile of NREM and REM sleep were unaffected. Control animals, injected with scrambled siRNA, had no sleep changes after injection. Quantification of the knockdown revealed that unilateral microinjection of siRNAs targeting OxR1 into the rat LC on two consecutive days induced a 45.5% reduction of OxR1 mRNA in the LC 2 days following the injections when compared with the contralateral side receiving injections of control (scrambled) siRNAs. This reduction disappeared 4 days after injection. Similarly, unilateral injection of OxR1 siRNA into the LC revealed a marked (33.5%) reduction of OxR1 staining 2 days following injections. In contrast, both the mRNA level and immunohistochemical staining for tyrosine hydroxylase were unaffected. The results indicate that a modest knockdown of OxR1 is sufficient to induce observable sleep changes. Moreover, orexin neurons, by acting on OxR1 in the LC, play a role in the diurnal gating of REM sleep.

Indexed as

DarknessGene Knockdown TechniquesAnimalsBehavior, AnimalElectroencephalographyIntracellular Signaling Peptides and ProteinsLocus CoeruleusMaleMicroinjectionsNeuropeptidesOrexin ReceptorsOrexinsRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledReceptors, NeuropeptideIntracellular Signaling Peptides and ProteinsNeuropeptidesOrexin ReceptorsOrexinsReceptors, G-Protein-CoupledReceptors, NeuropeptideRNA, Small Interfering

Identifiers

PMID21089218
PMCPMC3058252
OpenAlexW1896002679

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.