Exposure of Pregnant Rats to Restricted Feeding Schedule Synchronizes the SCN Clocks of Their Fetuses under Constant Light but Not under a Light-Dark Regime

Abstract

The circadian clock in the suprachiasmatic nucleus (SCN) develops gradually during the prenatal and early postnatal period. In the rat, this period lasts from around the 15th day of gestation until the 10th day of postnatal development. The circadian system of fetuses and newborn pups is entrained mostly by nonphotic maternal cues during prenatal and early postnatal development. The aim of the present study was to ascertain whether exposure of pregnant rats to a restricted feeding (RF) regime was able to entrain the circadian clock in the SCN of their fetuses during the prenatal period. The potency of RF as an entraining cue was tested under conditions when pregnant rats were entrained to an external light/dark (LD) cycle as well as under conditions when the external timing signal was lacking, i.e., under constant light (LL). The control groups were fed ad libitum and the experimental groups had restricted access to food for 6 h during their resting time throughout pregnancy. Daily profiles of Avp and c-fos gene expression were examined by in situ hybridization in the SCN of 1-day-old pups. The data demonstrated that RF in pregnant rats kept under LD cycle did not notably affect the daily rhythms of c-fos and Avp expression in the SCN of pups. The SCN profiles of Avp and c-fos gene expression did not exhibit circadian rhythms in pups born to mothers maintained in LL and fed ad libitum, likely due to desynchrony among the pups within a litter. However, RF in the pregnant rats kept under LL restored the circadian rhythmicity of c-fos and Avp expression in the SCN of their newborn pups. The results suggest that the fetal SCN clock is dominantly entrained by rhythmic signals from the maternal SCN. However, under conditions when the rhythmic signaling might be lacking, such as LL, regular food intake of the mothers may also play an important role in synchronization of the fetal SCN clock during prenatal ontogenesis.

Keywords

suprachiasmatic nucleus maternal entrainment restricted food ontogenesis rat

References

Aton SJ and Herzog ED ( 2005) Come together, right…now: synchronization of rhythms in a mammalian circadian clock. Neuron 48:531-534.

Burbach JP , Luckman SM , Murphy D. , and Gainer H. ( 2001) Gene regulation in the magnocellular hypothalamoneurohypophysial system. Physiol Rev 81:1197-1267.

Damiola F. , Le Minh N. , Preitner N. , Kornmann B. , Fleury-Olela F. , and Schibler U. ( 2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus . Genes Dev 14:2950-2961.

Davis FC and Gorski RA ( 1985) Development of hamster circadian rhythms, I: within-litter synchrony of mother and pup activity rhythms at weaning. Biol Reprod 33: 353-362.

Deery MJ , Maywood ES , Chesham JE , Sladek M. , Karp NA , Green EW , Charles PD , Reddy AB , Kyriacou CP , Lilley KS , et al. (2009) Proteomic analysis reveals the role of synaptic vesicle cycling in sustaining the suprachiasmatic circadian clock. Curr Biol 19:2031-2036.

Dolatshad H. , Cary AJ , and Davis FC ( 2010) Differential expression of the circadian clock in maternal and embryonic tissues of mice. PLoS One 5:e9855.

El-Hennamy R. , Matějů K. , Bendová Z. , Sosniyenko S. , and Sumová A. (2008) Maternal control of the fetal and neonatal rat suprachiasmatic nucleus. J Biol Rhythms 23: 435-444.

Hara R. , Wan K. , Wakamatsu H. , Aida R. , Moriya T. , Akiyama M. , and Shibata S. ( 2001) Restricted feeding entrains liver clock without participation of the suprachiasmatic nucleus. Genes Cells 6:269-278.

Hastings MH , Reddy AB , and Maywood ES ( 2003) A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci 4:649-661.

10.

Iwasaki Y. , Oiso Y. , Saito H. , and Majzoub JA ( 1997) Positive and negative regulation of the rat vasopressin gene promoter. Endocrinology 138:5266-5274.

11.

Ji Y. , Qin Y. , Shu H. , and Li X. ( 2010) Methylation analyses on promoters of mper1, mper2, and mcry1 during perinatal development. Biochem Biophys Res Commun 391: 1742-1747.

12.

Kováčiková Z. , Sládek M. , Bendová Z. , Illnerová H. , and Sumová A. ( 2006) Expression of clock and clock-driven genes in the rat suprachiasmatic nucleus during late fetal and early postnatal development . J Biol Rhythms 21:140-148.

13.

Landry GJ , Simon MM , Webb IC , and Mistlberger RE ( 2006) Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats. Am J Physiol Regul Integr Comp Physiol 290:R1527-1534.

14.

Li X. and Davis FC ( 2005) Developmental expression of clock genes in the syrian hamster. Brain Res Dev Brain Res 158:31-40.

15.

Mistlberger RE (2009) Food-anticipatory circadian rhythms: concepts and methods. Eur J Neurosci 30:1718-1729.

16.

Moore RY ( 1991) Development of the suprachiasmatic nucleus. In Suprachiasmatic Nucleus: The Mind’s Clock, Klein DC , Moore RY , and Repperts SM , eds, pp 197-216. New York: Oxford University Press.

17.

Moore RY and Bernstein ME ( 1989) Synaptogenesis in the rat suprachiasmatic nucleus demonstrated by electron microscopy and synapsin immunoreactivity. J Neurosci 9:2151-2162.

18.

Ohta H. , Xu S. , Moriya T. , Iigo M. , Watanabe T. , Nakahata N. , Chisaka H. , Hanita T. , Matsuda T. , Ohura T. , et al. (2008) Maternal feeding controls fetal biological clock. PLoS One 3:e2601.

19.

Ohta H. , Yamazaki S. , and McMahon DG ( 2005) Constant light desynchronizes mammalian clock neurons . Nat Neurosci 8:267-269.

20.

Pittendrigh CL ( 1981) Circadian systems: entrainment. In Handbook of Behavioral Neurology, Vol. 4, J Aschoff , ed, pp 95-124. New York: Plenum .

21.

Pittendrigh CS ( 1976) Circadian clocks: What are they? In The Molecular Basis of Circadian Rhythms, Hastings JW , Schweiger HG , eds, pp 11-48. Berlin : Dahlem Konferenzen.

22.

Reppert SM and Schwartz WJ ( 1984) The suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14c-labeled deoxyglucose. J Neurosci 4:1677-1682.

23.

Reppert SM and Schwartz WJ ( 1986) Maternal suprachiasmatic nuclei are necessary for maternal coordination of the developing circadian system. J Neurosci 6: 2724-2729.

24.

Reppert SM and Uhl GR ( 1987) Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development . Endocrinology 120:2483-2487.

25.

Reppert SM and Weaver DR ( 2001) Molecular analysis of mammalian circadian rhythms . Annu Rev Physiol 63: 647-676.

26.

Segall LA , Verwey M. , and Amir S. ( 2008) Timed restricted feeding restores the rhythms of expression of the clock protein, period2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in adrenalectomized rats . Neuroscience 157: 52-56.

27.

Shearman LP , Sriram S. , Weaver DR , Maywood ES , Chaves I. , Zheng B. , Kume K. , Lee CC , van der Horst GT , Hastings MH , et al. (2000) Interacting molecular loops in the mammalian circadian clock. Science 288:1013-1019.

28.

Sheward WJ , Maywood ES , French KL , Horn JM , Hastings MH , Seckl JR , Holmes MC , and Harmar AJ ( 2007) Entrainment to feeding but not to light: circadian phenotype of vpac2 receptor-null mice. J Neurosci 27: 4351-4358.

29.

Shibata S. and Moore RY ( 1987) Development of neuronal activity in the rat suprachiasmatic nucleus. Brain Res 431:311-315.

30.

Shibata S. and Moore RY ( 1988) Development of a fetal circadian rhythm after disruption of the maternal circadian system. Brain Res 469:313-317.

31.

Shimomura H. , Moriya T. , Sudo M. , Wakamatsu H. , Akiyama M. , Miyake Y. , and Shibata S. ( 2001) Differential daily expression of per1 and per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice. Eur J Neurosci 13:687-693.

32.

Sládek M. , Rybová M. , Jindráková Z. , Zemanová Z. , Polidarová L. , Mrnka L. , O’Neill J. , Pácha J. , and Sumová A. (2007) Insight into the circadian clock within rat colonic epithelial cells. Gastroenterology 133: 1240-1249.

33.

Sládek M. , Sumová A. , Kováčiková Z. , Bendová Z. , Laurinová K. , and Illnerová H. ( 2004) Insight into molecular core clock mechanism of embryonic and early postnatal rat suprachiasmatic nucleus. Proc Natl Acad Sci U S A 101: 6231-6236.

34.

Stokkan KA , Yamazaki S. , Tei H. , Sakaki Y. , and Menaker M. ( 2001) Entrainment of the circadian clock in the liver by feeding . Science 291:490-493.

35.

Takahashi JS , Hong HK , Ko CH , and McDearmon EL ( 2008) The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 9:764-775.

36.

Weaver DR and Reppert SM ( 1989) Periodic feeding of SCN-lesioned pregnant rats entrains the fetal biological clock. Brain Res Dev Brain Res 46:291-296.