TY - JOUR
T1 - Assessment of circadian rhythms in humans
T2 - Comparison of real-time fibroblast reporter imaging with plasma melatonin
AU - Hasan, Sibah
AU - Santhi, Nayantara
AU - Lazar, Alpar S.
AU - Slak, Ana
AU - Lo, June
AU - Von Schantz, Malcolm
AU - Archer, Simon N.
AU - Johnston, Jonathan D.
AU - Dijk, Derk Jan
N1 - Funding information:
UK Biotechnology and Biological Sciences Research Council. Grant Number: BB/F022883/1
PY - 2012/6
Y1 - 2012/6
N2 - We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±SD) were longer than in vivo periods (31 participants, 24.16±0.17 h; P<0.0001) but did not differ between PER3 genotypes (P>0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate (P>0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin (P<0.05) at baseline and with diurnal preference (P<0.05). Individual circadian rhythms can be reliably assessed in fibroblasts but may not correlate with physiological rhythms driven by the central circadian pacemaker.
AB - We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±SD) were longer than in vivo periods (31 participants, 24.16±0.17 h; P<0.0001) but did not differ between PER3 genotypes (P>0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate (P>0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin (P<0.05) at baseline and with diurnal preference (P<0.05). Individual circadian rhythms can be reliably assessed in fibroblasts but may not correlate with physiological rhythms driven by the central circadian pacemaker.
KW - Bmal1
KW - Clock genes
KW - Lentivirus
KW - PER3
KW - Sleep
UR - http://www.scopus.com/inward/record.url?scp=84861778707&partnerID=8YFLogxK
U2 - 10.1096/fj.11-201699
DO - 10.1096/fj.11-201699
M3 - Article
C2 - 22371527
AN - SCOPUS:84861778707
SN - 0892-6638
VL - 26
SP - 2414
EP - 2423
JO - FASEB Journal
JF - FASEB Journal
IS - 6
ER -