Jetlaginducedinternaldesynchronizationisassociatedwithdeficitsinadultneurogenesisinmouse
hippocampus.
K.L.Correia,1 G.Kim,1 S.Tjho2,E.M.Gibson,2K.Wright,1C.Wasserman,1 L.J.Kriegsfeld2,M.E.Harrington1
1DepartmentofNeuroscience,SmithCollege,Northampton,MA
2DepartmentofPsychologyandHelenWillsNeuroscienceInstitute,UCBerkeley,Berkeley,CA
Chronic4hphaseadvancesoftheLDcycle
causelittleinternaldesynchrony.
Introduction
In2008,theDanishgovernmentgrantedfinancialcompensationfordozensofits
femalecitizenswho1)hadahistoryofworkingovernightshiftsatleastonceperweekand
2)hadcontractedbreastcancer.Thisconnectionbetweenabnormalworkschedulesand
heightenedcancerincidenceisnotlimitedtotheDanishpopulation:approximately15
20%ofworkersinalldevelopednationsperformperiodicnightorrotatingshiftworkor
areinvolvedinfrequenttransmeridiantravel.Severalepidemiologicstudieshaveshown
thatrotatingshiftworkers,flightattendants,andotherswithfrequentexposuretolightat
nighthavesufferedfromvarioushealthrelatedmaladiesrangingfromcardiovascular
diseasetoprostatecancer(3).Inordertounderstandthepossiblecarcinogenicinfluence
ofabnormaldailycycles,itisimportanttofirstbecomefamiliarwithcircadianrhythms
andtheeffectsofcircadiandisruptiononinternalhomeostasis.
Jetlagmaybluntadultneurogenesis.
Control:
4hphaseadvanceshiftingschedule
Neurogenesis is the birth of new neurons.
Control
Day1
Day3
35
30
Chronic8hphaseadvancesoftheLDcycle
causemoreinternaldesynchrony.
Shiftworkandfrequentjetlagareassociatedwithavarietyofhealthmaladies.For
example,onereportfoundthatairlineworkerswithfrequentjetlagexhibittemporallobe
atrophyandcognitivedeficits(1,2).WestEastboundtravel(i.e.advancesoftheLDcycle)
ismoredetrimentalthanEastWestboundtravel(phasedelays).Wedeterminedifphase
advancesoftheLDcycleimpactadulthippocampalneurogenesisinmice.
25
20
Percent
Neurogenesis
8hphaseadvances:
15
10
5
0
1
control
Hypothesis
Chronic8hphaseadvancescausebehavioralandinternaldesynchrony.However,byday3ofthefinal
LDcycle,theSCNisabletocompletethe8hshiftbutperipheralorganscontinuetolag.Thecircular
Raleighplotsshow1)normalSCN:peripheralorganphaserelationshipsfromanimalskeptina
constantLDcycleand2)abnormalSCN:POphaserelationshipsonday1ofthefourth8hadvance.
Weproposethatnegativehealtheffectsduetojetlagmayresultfroma
disruptioninthephaserelationshipofthemastercircadianclockinthe
suprachiasmaticnuclei(SCN)ofthehypothalamusandperipheralorgans.
2
weekly 8h
advances
Percentneurogenesisincontrolversusweekly8hphase
advancedmice.
Animalstreatedwith8hadvanceshiftsshowedreduced
hippocampalneurogenesisrelativetocontrolanimals.Cells
arecolabeledwithBrdUandNeuN.
Green=BrdU; Red=NeuN; Blue=GFAP
Rapid8hphaseadvancesoftheLDcycle
causethemost internaldesynchrony.
Materials&Methods
A
c57/BL6and
Per2Luc
females,aged
24months
Spleen
Esophagus
Oxyluciferin
AMP
CO2
Light
8hphaseadvance
weeklyorrapid
Chronic4h
phaseadvances
Controlgroup
C
Thymus
Luciferin Luciferase
ATP
Mg++
O2
Conclusions
Thisstudyindicatesthatchronicjetlagcannegativelyimpactthematurationofneurons
intheadulthippocampus.Futurestudieswillexperimentallyexaminetheconsequences
ofdisruptionofphaserelationshipsbetweentheSCNandperipheralorgansonmental
andphysiologicalhealth.
Acknowledgements
B
ThisworkissupportedbytheSmithCollegeTomlinsonFundandthe
McKinleyHonorsFellowship.
References
Per2Luc: bioluminescenceanalysis
C57s: bromodeoxyuridine(BrdU)injections21dayspriortocull
Immunohistochemistry:BrdU,PCNA,GFAP,NeuN
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A) Sample actogram from a mouse undergoing frequent 8h phase advances of the
LD cycle. B) Raleigh plot demonstrating mean tissue values relative to acrophase
on the final day of the previous shift. C) Chart of various levels of internal desynchrony,
highlighting phase values relative to SCN phase for a given experimental condition.
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