Maternal Dietary Restriction Alters Offspring’s Sleep Homeostasis

Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD) or 50% dietary restriction (DR) groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8–9 weeks), we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (NREM) sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM) sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor α (Pparα) and brain-specific carnitine palmitoyltransferase 1 (Cpt1c) mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure.

妊娠期营养状态可影响胎儿的生长发育。本研究假设，妊娠期膳食不足会对子代的睡眠结构和/或睡眠稳态产生影响。实验将妊娠雌性小鼠自妊娠第12天至分娩阶段，随机分为两组：对照组（自由采食，ad libitum, AD）与50%膳食限制（dietary restriction, DR）组。分娩完成后，母鼠恢复自由采食标准饲料。子代小鼠断奶后，同样以自由采食方式喂养至成年。待子代小鼠成长至8~9周龄的成年期时，研究人员对其开展睡眠记录。尽管子代小鼠出生时体重显著降低，但在出生后3天即可恢复至正常水平。在24小时监测周期内，DR组小鼠的非快速眼动（non-rapid eye movement, NREM）睡眠期间的脑电图（electroencephalogram, EEG）慢波活动（slow wave activity, SWA）显著增强，且未改变昼夜节律模式，也未影响觉醒、NREM睡眠与快速眼动（rapid eye movement, REM）睡眠的总时长。此外，在经历6小时睡眠剥夺后，DR组小鼠的EEG-SWA反弹现象更为显著，同时面对外部刺激时的觉醒阈值更高。成年DR组子代小鼠的下丘脑中，两项参与脂质代谢的基因——过氧化物酶体增殖物激活受体α（peroxisome proliferator-activated receptor α, Pparα）与脑特异性肉碱棕榈酰转移酶1（brain-specific carnitine palmitoyltransferase 1, Cpt1c）的mRNA表达水平出现小幅但具有统计学意义的升高。妊娠期膳食不足可能会影响子代的睡眠稳态，使子代表现出更强的睡眠压力。