Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats.
Although sleep complaints are very common among pregnant women, the potential adverse effects of sleep disturbance on the offspring are not well studied. Growing evidence suggests that maternal stress can induce an inflammatory environment on the fetal development. But people are not sure about the consequences of prenatal stress such as the inflammatory responses induced by maternal sleep deprivation (MSD). In the present study, we investigated the effects of MSD on long-term behavioral and cognitive consequences in offspring and its underlying inflammatory response pathway. The pregnant Wistar rats received prolonged sleep deprivation (72h) on gestational day (GD) 4, 9, and 18, respectively. The post-natal day (PND) 21 offspring showed impaired hippocampus-dependent spatial learning and memory in the Morris Water Maze task and anhedonia in sucrose preference experiment. Quantification of BrdU(+) and DCX(+) cells revealed a significant decrease in hippocampus neurogenesis in prepuberty offspring, especially for the late MSD (GD 18) group. Real-time RT-PCR showed that after MSD, the expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) increased in the hippocampus of offspring on PND 1, 7, 14 and 21, whereas anti-inflammatory cytokine IL-10 reduced at the same time. Immunofluorescence found that the cells of activated microglia were higher in the brains of MSD offspring. Taken together, these results suggested that the MSD-induced inflammatory response is an important factor for neurogenesis impairment and neurobehavioral outcomes in prepuberty offspring.
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
Qiuying
Q
Zhao
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Cheng
C
Peng
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
Xiaohui
X
Wu
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
Yubo
Y
Chen
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
Cheng
C
Wang
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: youzili@uestc.edu.cn.
Zili
Z
You
D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005518:Food Preferences / Q000502:physiology; D005865:Gestational Age; D006624:Hippocampus / Q000503:physiopathology*; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012744:Sex Ratio; D012892:Sleep Deprivation / Q000150:complications*; D013395:Sucrose / Q000008:administration & dosage
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016753:Interleukin-10; D013395:Sucrose
Inflammatory response; Microglial activation; Neurogenesis; Offspring; Pregnancy; Sleep deprivation