0043 BDNF Genotype Modulates Circadian Response to Simulated Nightwork in IL-6

Abstract

Abstract Introduction Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and may be involved in sleep and circadian regulation. The BDNF gene has a single nucleotide polymorphism (Val66Met) resulting in decreased BDNF secretion. The Met allele is associated with reduced nocturnal slow wave activity following sleep loss, and may also enable more flexible adaptation to circadian misalignment. We used IL-6, a pleiotropic cytokine with biphasic circadian secretion, to compare the response of Val and Met carriers to circadian misalignment. Methods 15 healthy men (26.7±4.9y) participated in a 16-day laboratory study of simulated nightwork with two nighttime duty cycles and an intervening 58h restart break. The study began with two baseline 10h time in bed (TIB) nighttime sleep opportunities (22:00-08:00) and a 5h TIB afternoon nap (15:00-20:00). Each duty cycle consisted of five nighttime waking periods and four 10h TIB daytime sleeps (10:00-20:00). The restart break began with a 5h TIB morning nap (10:00-15:00), followed by two 10h TIB nighttime sleeps (22:00-08:00). The middle two daytime sleep periods from each duty cycle were monitored polysomnographically and visually scored. During the baseline and restart periods, blood samples were collected at 08:25 and then at 2h intervals until 20:00. Plasma IL-6 was measured by means of ELISA. BDNF Val66Met genotype was determined from whole blood. Results The genotype distribution was in Hardy-Weinberg equilibrium (Val/Val:5; Val/Met:10; Met/Met:0). On average, Met carriers slept 52.2min longer (p=0.052) and displayed 27.7min more REM (p=0.013) than Val/Val subjects during the 10h TIB daytime sleeps. Baseline IL-6 concentrations were similar between genotypes. However, during the restart break, Val/Met subjects showed reduced IL-6 compared to baseline and to Val/Val subjects (p=0.022). Conclusion BDNF Val66Met heterozygotes exhibited blunted IL-6 levels following simulated nightwork, suggesting this genotype experienced a substantial circadian shift and/or altered response to sleep loss associated with daytime sleep. Support FMCSA award DTMC75-07-D-00006; Elliot D. Weitzman, M.D. Research Grant from the Sleep Research Society Foundation.