Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
PLoS One. 2020 Apr 17;15(4):e0231140. doi: 10.1371/journal.pone.0231140. eCollection 2020.
Functional circadian timekeeping is necessary for homeostatic control of the immune system and appropriate immune responsiveness. Disruption of natural light-dark cycles, through light at night (LAN), impairs innate and adaptive immune responses in nocturnal rodents. These altered immune responses are associated with disrupted endogenous gene transcriptional and endocrine cycles. However, few studies have addressed the multigenerational consequences of systemic circadian rhythm disruption. We hypothesized that parental exposure to dim LAN (dLAN) would alter innate immune and sickness responses to an endotoxin challenge in adult offspring gestated and reared in dark nights. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 8 weeks, then paired, mated, and thereafter housed under dark nights. Maternal exposure to dLAN prior to conception impaired febrile responses and increased splenic il-1 production in response to LPS in male offspring. Paternal pre-conception dLAN dampened offspring tnf-α expression in the hypothalamus, reduced serum bactericidal capacity, and dark phase locomotor activity. These changes occurred despite offspring being conceived, gestated, and reared under standard dark night conditions. Overall, these data suggest that dLAN has intergenerational effects on innate immunity and sickness responses.
功能性的昼夜节律计时对于免疫系统的内稳态控制和适当的免疫反应是必要的。通过夜间的光线(LAN)破坏自然的明暗周期,会损害夜间啮齿动物的先天和适应性免疫反应。这些改变的免疫反应与内源性基因转录和内分泌周期的破坏有关。然而,很少有研究探讨系统性昼夜节律破坏的多代后果。我们假设,父母在暗夜间(dLAN)的暴露会改变成年后代在暗夜间孕育和饲养时对内毒素挑战的先天免疫和疾病反应。成年雄性和雌性的仓鼠被暴露在黑暗的夜晚(DARK)或 dLAN(~5 lux)中 8 周,然后配对、交配,然后在黑暗的夜晚下饲养。在受孕前,母亲在 dLAN 下的暴露会损害雄性后代对 LPS 的发热反应,并增加脾脏白细胞介素-1 的产生。父亲在受孕前的 dLAN 减弱了后代在下丘脑的肿瘤坏死因子-α表达,降低了血清杀菌能力,并减少了暗期的运动活动。尽管后代在标准的暗夜间条件下受孕、孕育和饲养,但这些变化仍然发生了。总的来说,这些数据表明,dLAN 对先天免疫和疾病反应有代际影响。