Document Detail

A neuropeptide speeds circadian entrainment by reducing intercellular synchrony.
MedLine Citation:
PMID:  24167276     Owner:  NLM     Status:  MEDLINE    
Shift work or transmeridian travel can desynchronize the body's circadian rhythms from local light-dark cycles. The mammalian suprachiasmatic nucleus (SCN) generates and entrains daily rhythms in physiology and behavior. Paradoxically, we found that vasoactive intestinal polypeptide (VIP), a neuropeptide implicated in synchrony among SCN cells, can also desynchronize them. The degree and duration of desynchronization among SCN neurons depended on both the phase and the dose of VIP. A model of the SCN consisting of coupled stochastic cells predicted both the phase- and the dose-dependent response to VIP and that the transient phase desynchronization, or "phase tumbling", could arise from intrinsic, stochastic noise in small populations of key molecules (notably, Period mRNA near its daily minimum). The model also predicted that phase tumbling following brief VIP treatment would accelerate entrainment to shifted environmental cycles. We tested this using a prepulse of VIP during the day before a shift in either a light cycle in vivo or a temperature cycle in vitro. Although VIP during the day does not shift circadian rhythms, the VIP pretreatment approximately halved the time required for mice to reentrain to an 8-h shifted light schedule and for SCN cultures to reentrain to a 10-h shifted temperature cycle. We conclude that VIP below 100 nM synchronizes SCN cells and above 100 nM reduces synchrony in the SCN. We show that exploiting these mechanisms that transiently reduce cellular synchrony before a large shift in the schedule of daily environmental cues has the potential to reduce jet lag.
Sungwon An; Rich Harang; Kirsten Meeker; Daniel Granados-Fuentes; Connie A Tsai; Cristina Mazuski; Jihee Kim; Francis J Doyle; Linda R Petzold; Erik D Herzog
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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:  2013-10-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-13     Completed Date:  2014-01-08     Revised Date:  2014-06-04    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E4355-61     Citation Subset:  IM    
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MeSH Terms
Biological Clocks / drug effects,  physiology*
Circadian Rhythm / drug effects,  physiology*
Dose-Response Relationship, Drug
Luminescent Measurements
Models, Biological*
Motor Activity / physiology
Period Circadian Proteins / metabolism
Signal Transduction / physiology*
Suprachiasmatic Nucleus / physiology*
Vasoactive Intestinal Peptide / metabolism*,  pharmacology
Grant Support
Reg. No./Substance:
0/Period Circadian Proteins; 37221-79-7/Vasoactive Intestinal Peptide

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

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