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Programming effects of maternal stress on the circadian system of adult offspring

Title
Programming effects of maternal stress on the circadian system of adult offspring
Authors
Yun, SeongsikLee, Eun JeongChoe, Han KyoungSon, Gi HoonKim, KyungjinChung, Sooyoung
DGIST Authors
Yun, Seongsik; Lee, Eun Jeong; Choe, Han Kyoung; Son, Gi Hoon; Kim, Kyungjin; Chung, Sooyoung
Issue Date
2020-03
Citation
Experimental and Molecular Medicine, 52(3), 473-484
Type
Article
Article Type
Article
Keywords
MOUSE SUPRACHIASMATIC NUCLEUSREV-ERB-ALPHAGENE-EXPRESSIONRHYTHMSGLUCOCORTICOIDSTRANSCRIPTIONOSCILLATIONIMPAIRMENTACTIVATIONALTERS
ISSN
1226-3613
Abstract
Maternal stress has long-lasting influences on the brain functions of offspring, and several brain regions have been proposed to mediate such programming. Although perinatal programming of crosstalk between the circadian and stress systems has been proposed, the functional consequences of prenatal stress on the circadian system and the underlying mechanisms remain largely unknown. Therefore, we investigated whether exposing pregnant mice to chronic restraint stress had prolonged effects on the suprachiasmatic nucleus (SCN), which bears the central pacemaker for mammalian circadian rhythms, of offspring. SCN explants from maternally stressed mice exhibited altered cyclic expression patterns of a luciferase reporter under control of the mouse Per1 promoter (mPer1::LUC), which manifested as a decreased amplitude and impaired stability of the rhythm. Bioluminescence imaging at the single-cell level subsequently revealed that impaired synchrony among individual cells was responsible for the impaired rhythmicity. These intrinsic defects appeared to persist during adulthood. Adult male offspring from stressed mothers showed advanced-phase behavioral rhythms with impaired stability as well as altered clock gene expression in the SCN. In addition to affecting the central rhythm, maternal stress also had prolonged influences on the circadian characteristics of the adrenal gland and liver, as determined by circulating corticosterone levels and hepatic glycogen content, and on canonical clock gene mRNA expression in those tissues. Taken together, our findings suggest that the SCN is a key target of the programming effects of maternal stress. The widespread effects of circadian disruptions caused by a misprogrammed clock may have further impacts on metabolic and mental health in later life. © 2020, The Author(s).
URI
http://hdl.handle.net/20.500.11750/11593
DOI
10.1038/s12276-020-0398-9
Publisher
Nature Publishing Group
Related Researcher
  • Author Choe, Han Kyoung Laboratory of Animal Behavior and Circadian rhythm
  • Research Interests Modulation of neural circuit; Circadian regulation of behavior and perception; Neurotechnology
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Animal Behavior and Circadian rhythm1. Journal Articles


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