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Stress affects expression of the clock gene Bmal1 in the suprachiasmatic nucleus of neonatal rats via glucocorticoid‐dependent mechanism
Author(s) -
Olejníková L.,
Polidarová L.,
Sumová A.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13020
Subject(s) - suprachiasmatic nucleus , mechanism (biology) , glucocorticoid , nucleus , clock , neuroscience , medicine , endocrinology , biology , circadian rhythm , microbiology and biotechnology , chemistry , circadian clock , physics , quantum mechanics
Aim The reactivity of the circadian clock in the suprachiasmatic nuclei ( SCN ) to stressful stimuli has been controversial but most studies have confirmed the resilience of the SCN to stress. We tested the hypothesis that during a critical period shortly after birth, the developing SCN clock is affected by glucocorticoids. Methods Mothers of 2 rat strains with different sensitivities to stress, that is Wistar rats and spontaneously hypertensive rats ( SHR ), and their pups were exposed to stressful stimuli every day from delivery, and clock gene expression profiles were detected in the 4‐day‐old pups’ SCN . Levels of glucocorticoids in plasma were measured by LC ‐ MS / MS . The glucocorticoid receptors antagonist mifepristone was administered to pups to block the effect of the glucocorticoids. Results The glucocorticoid receptors were detected at the mRNA and protein levels in the SCN of 4‐day‐old pups. The exposure of mothers to stressful stimuli elevated their plasma glucocorticoid levels. In Wistar rat pups, combination of daily maternal stress with their manipulation increased the plasma glucocorticoid levels and shifted the Bmal1 rhythm in the SCN which was completely blocked by mifepristone. In contrast, in SHR pups, maternal stress on its own caused phase shift of the Bmal1 expression rhythm in the SCN but the effect was mediated via glucocorticoid‐independent mechanism. The Per1 and Per2 expression profiles remained phase‐locked to the light/dark cycle. Conclusion The results demonstrate that the SCN is sensitive to stressful stimuli early after birth in pups maintained under light/dark conditions and the effect is mediated via glucocorticoid‐dependent pathways.