Gender associated circadian oscillations of the clock genes in rat choroid plexus

Abstract

It is well-documented that circadian rhythms are controlled by the circadian master clock of the mammalian brain, located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN clockwork is a cell autonomous mechanism consisting of a series of interlocked transcriptional/post-translational feedback loops. In turn, the SCN controls the seasonal rhythmicity of various biological processes, in particular the secretion pattern of hormones. Although the effects of gonadal hormones on circadian rhythmicity are clearly established, how the SCN integrates and regulates these hormonal stimuli remains unknown. We have previously found that clock genes are expressed in the choroid plexus (CP). Therefore, we compared the circadian expression of these genes in female and male rat CP. We show that there is a 24-h rhythm in the expression of Per2 and Cry2 in males and females. Bmal1 and Per1 expression also varied along the day, but only in females. Bmal1, Clock and Per1 mRNA did not show any significant differences in the CP of males. Moreover, data from cultured CP cells collected at different timepoints revealed significant circadian rhythms in mRNA abundance of Bmal1, Clock and Per2. In conclusion, our data show that the rat CP expresses all canonical clock genes and that their circadian expression differs between genders suggesting that hormones can regulate circadian rhythmicity in CP.

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References

  1. Abe H, Honma S, Namihira M, Tanahashi Y, Ikeda M, Honma K (1998) Circadian rhythm and light responsiveness of BMAL1 expression, a partner of mammalian clock gene Clock, in the suprachiasmatic nucleus of rats. Neurosci Lett 258:93–96

    Article  CAS  PubMed  Google Scholar 

  2. Abe M, Herzog ED, Yamazaki S, Straume M, Tei H, Sakaki Y, Menaker M, Block GD (2002) Circadian rhythms in isolated brain regions. J Neurosci 22:350–356

    CAS  PubMed  Google Scholar 

  3. Albrecht U (2012) Timing to perfection: the biology of central and peripheral circadian clocks. Neuron 74:246–260

    Article  CAS  PubMed  Google Scholar 

  4. Alvarez-Lopez C, Cernuda-Cernuda R, Garcia-Fernandez JM (2006) The mPer1 clock gene expression in the rd mouse suprachiasmatic nucleus is affected by the retinal degeneration. Brain Res 1087:134–141

    Article  CAS  PubMed  Google Scholar 

  5. Borgs L, Beukelaers P, Vandenbosch R, Nguyen L, Moonen G, Maquet P, Albrecht U, Belachew S, Malgrange B (2009) Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus. BMC Neurosci 10:30

    Article  PubMed Central  PubMed  Google Scholar 

  6. Chilov D, Hofer T, Bauer C, Wenger RH, Gassmann M (2001) Hypoxia affects expression of circadian genes PER1 and CLOCK in mouse brain. FASEB J 15:2613–2622

    Article  CAS  PubMed  Google Scholar 

  7. Chodobski A, Szmydynger-Chodobska J (2001) Choroid plexus: target for polypeptides and site of their synthesis. Microsc Res Tech 52:65–82

    Article  CAS  PubMed  Google Scholar 

  8. Daan S, Damassa D, Pittendrigh CS, Smith ER (1975) An effect of castration and testosterone replacement on a circadian pacemaker in mice (Mus musculus). Proc Natl Acad Sci USA 72:3744–3747

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. De La Iglesia HO, Blaustein JD, Bittman EL (1999) Oestrogen receptor-alpha-immunoreactive neurones project to the suprachiasmatic nucleus of the female Syrian hamster. J Neuroendocrinol 11:481–490

    Article  Google Scholar 

  10. Emerich DF, Skinner SJ, Borlongan CV, Vasconcellos AV, Thanos CG (2005) The choroid plexus in the rise, fall and repair of the brain. BioEssays 27:262–274

    Article  CAS  PubMed  Google Scholar 

  11. Fahrenkrug J, Hannibal J, Georg B (2008) Diurnal rhythmicity of the canonical clock genes Per1, Per2 and Bmal1 in the rat adrenal gland is unaltered after hypophysectomy. J Neuroendocrinol 20:323–329

    Article  CAS  PubMed  Google Scholar 

  12. Falcao AM, Marques F, Novais A, Sousa N, Palha JA, Sousa JC (2012) The path from the choroid plexus to the subventricular zone: go with the flow! Front Cell Neurosci 6:34

    Article  PubMed Central  PubMed  Google Scholar 

  13. Guilding C, Piggins HD (2007) Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci 25:3195–3216

    Article  PubMed  Google Scholar 

  14. Guilding C, Hughes AT, Brown TM, Namvar S, Piggins HD (2009) A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus. Mol Brain 2:28

    Article  PubMed Central  PubMed  Google Scholar 

  15. Hastings MH, Field MD, Maywood ES, Weaver, Reppert SM (1999) Differential regulation of mPER1 and mTIM proteins in the mouse suprachiasmatic nuclei: new insights into a core clock mechanism. J Neurosci 19:RC11

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Johanson C, Stopa E, McMillan P, Roth D, Funk J, Krinke G (2011) The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and brain: toxicologic/pathologic phenomena, periventricular destabilization, and lesion spread. Toxicol Pathol 39:186–212

    Article  PubMed  Google Scholar 

  18. Karatsoreos IN, Silver R (2007) Minireview: the neuroendocrinology of the suprachiasmatic nucleus as a conductor of body time in mammals. Endocrinology 148:5640–5647

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Karman BN, Tischkau SA (2006) Circadian clock gene expression in the ovary: effects of luteinizing hormone. Biol Reprod 75:624–632

    Article  CAS  PubMed  Google Scholar 

  20. Ko CH, Takahashi JS (2006) Molecular components of the mammalian circadian clock. Hum Mol Genet 15(2):R271–R277

    Article  CAS  PubMed  Google Scholar 

  21. Kondratov RV, Chernov MV, Kondratova AA, Gorbacheva VY, Gudkov AV, Antoch MP (2003) BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. Genes Dev 17:1921–1932

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Kriegsfeld LJ, Silver R (2006) The regulation of neuroendocrine function: timing is everything. Horm Behav 49:557–574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Kwon I, Lee J, Chang SH, Jung NC, Lee BJ, Son GH, Kim K, Lee KH (2006) BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer. Mol Cell Biol 26:7318–7330

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Li Y, Chen J, Chopp M (2002) Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats. J Neurol Sci 193:137–146

    Article  PubMed  Google Scholar 

  25. Mohawk JA, Green CB, Takahashi JS (2012) Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445–462

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Mong JA, Baker FC, Mahoney MM, Paul KN, Schwartz MD, Semba K, Silver R (2011) Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci 31:16107–16116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Moore RY (1983) Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc 42:2783–2789

    CAS  PubMed  Google Scholar 

  28. Morin LP (1980) Effect of ovarian hormones on synchrony of hamster circadian rhythms. Physiol Behav 24:741–749

    Article  CAS  PubMed  Google Scholar 

  29. Murphy ZC, Pezuk P, Menaker M, Sellix MT (2013) Effects of ovarian hormones on internal circadian organization in rats. Biol Reprod 89:35

    Article  PubMed Central  PubMed  Google Scholar 

  30. Nakamura TJ, Sellix MT, Menaker M, Block GD (2008) Estrogen directly modulates circadian rhythms of PER2 expression in the uterus. Am J Physiol Endocrinol Metab 295:E1025–E1031

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Nielsen HS, Hannibal J, Knudsen SM, Fahrenkrug J (2001) Pituitary adenylate cyclase-activating polypeptide induces period1 and period2 gene expression in the rat suprachiasmatic nucleus during late night. Neuroscience 103:433–441

    Article  CAS  PubMed  Google Scholar 

  32. Okamura H, Miyake S, Sumi Y, Yamaguchi S, Yasui A, Muijtjens M, Hoeijmakers JH, van der Horst GT (1999) Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science 286:2531–2534

    Article  CAS  PubMed  Google Scholar 

  33. Panda S, Hogenesch JB (2004) It’s all in the timing: many clocks, many outputs. J Biol Rhythms 19:374–387

    Article  CAS  PubMed  Google Scholar 

  34. Perrin JS, Segall LA, Harbour VL, Woodside B, Amir S (2006) The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle. Proc Natl Acad Sci USA 103:5591–5596

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Quintela T, Alves CH, Goncalves I, Baltazar G, Saraiva MJ, Santos CR (2008) 5Alpha-dihydrotestosterone up-regulates transthyretin levels in mice and rat choroid plexus via an androgen receptor independent pathway. Brain Res 1229:18–26

    Article  CAS  PubMed  Google Scholar 

  37. Quintela T, Goncalves I, Carreto LC, Santos MA, Marcelino H, Patriarca FM, Santos CR (2013) Analysis of the effects of sex hormone background on the rat choroid plexus transcriptome by cDNA microarrays. PLoS ONE 8:e60199

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Rath MF, Rohde K, Moller M (2012) Circadian oscillations of molecular clock components in the cerebellar cortex of the rat. Chronobiol Int 29:1289–1299

    Article  CAS  PubMed  Google Scholar 

  39. Rath MF, Rohde K, Fahrenkrug J, Moller M (2013) Circadian clock components in the rat neocortex: daily dynamics, localization and regulation. Brain Struct Funct 218:551–562

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    Article  CAS  PubMed  Google Scholar 

  42. Sellix MT, Murphy ZC, Menaker M (2013) Excess androgen during puberty disrupts circadian organization in female rats. Endocrinology 154:1636–1647

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Tamaru T, Isojima Y, van der Horst GT, Takei K, Nagai K, Takamatsu K (2003) Nucleocytoplasmic shuttling and phosphorylation of BMAL1 are regulated by circadian clock in cultured fibroblasts. Genes Cells 8:973–983

    Article  CAS  PubMed  Google Scholar 

  45. Vida B, Hrabovszky E, Kalamatianos T, Coen CW, Liposits Z, Kallo I (2008) Oestrogen receptor alpha and beta immunoreactive cells in the suprachiasmatic nucleus of mice: distribution, sex differences and regulation by gonadal hormones. J Neuroendocrinol 20:1270–1277

    Article  CAS  PubMed  Google Scholar 

  46. Wunderer F, Kuhne S, Jilg A, Ackermann K, Sebesteny T, Maronde E, Stehle JH (2013) Clock gene expression in the human pituitary gland. Endocrinology 154(6):2046–2057

    Article  CAS  PubMed  Google Scholar 

  47. Yagita K, Tamanini F, Yasuda M, Hoeijmakers JH, van der Horst GT, Okamura H (2002) Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein. EMBO J 21:1301–1314

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T, Takumi T (2004) Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. BMC Mol Biol 5:18

    Article  PubMed Central  PubMed  Google Scholar 

  49. Yamaoka S (1980) Modification of circadian sleep rhythms by gonadal steroids and the neural mechanisms involved. Brain Res 185:385–398

    Article  CAS  PubMed  Google Scholar 

  50. Zhang L, Abraham D, Lin ST, Oster H, Eichele G, Fu YH, Ptacek LJ (2012) PKCgamma participates in food entrainment by regulating BMAL1. Proc Natl Acad Sci USA 109:20679–20684

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal—http://www.FCT.pt) project grants (PTDC/SAU-NEU/114800/2009) and COMPETE (PEst-C/SAU/UI0709/2011). Telma Quintela is a recipient of a FCT fellowship (SFRH/BPD/70781/2010).

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Quintela, T., Sousa, C., Patriarca, F.M. et al. Gender associated circadian oscillations of the clock genes in rat choroid plexus. Brain Struct Funct 220, 1251–1262 (2015). https://doi.org/10.1007/s00429-014-0720-1

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Keywords

  • Choroid plexus
  • Circadian rhythm
  • Sex hormones
  • Clock genes
  • Suprachiasmatic nucleus