Skip to main content

Advertisement

SpringerLink
Log in

Effect of melatonin on age induced changes in daily serotonin rhythms in suprachiasmatic nucleus of male Wistar rat

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The decline in physiological functions with aging may affect the ability of the SCN, the biological clock, circadian pacemaker to transmit rhythmic information to other neural target sites, and thereby modify the expression of biological rhythms resulting in circadian disorders. Neurotransmitter serotonin plays important role in the photic and non-photic regulation of circadian rhythms and is a precursor of neurohormone melatonin, an internal zeitgeber. To assess effects of aging on the functional integrity of circadian system, we studied daily serotonin rhythms in the SCN by measuring serotonin levels at variable time points in wide range of age groups such as 15 days, 1, 2, 3 (adult), 4, 6, 9, 12, 18 and 24 months old male wistar rats. Animals were maintained in light–dark conditions (LD; 12:12) two weeks prior to experiment. We report here that in 15 days, 1 and 2 months old rat SCN the mean serotonin level is low and daily serotonin rhythm is just beginning; at 3, 4 and 6 months, serotonin levels and rhythms are robust and at 9, 12, 18 and 24 months mean serotonin levels are low again and rhythm is becoming more disrupted. Previous studies have shown the 5-HT rhythmicity was established by 3 month in rat brain but disintegrated by 6 months of age. As melatonin, an endogenous synchronizer and an antiaging agent, declines with aging, the effects of exogenous melatonin administration on serotonin rhythmicity in SCN in 3, 6, 9 and 24 months old rats were studied to assess effects of aging on responsiveness to melatonin. Our studies indicated an age related loss of sensitivity to melatonin in the restoration of age induced changes in SCN serotonin amplitude and rhythmicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Baggs JE, Price TS, Di Tacchio L, Panda S, Fitz Gerald GA (2009) Network features of the mammalian circadian clock. PLoS Biol 7:563–575

    Article  CAS  Google Scholar 

  • Barnard AR, Nolan PM (2008) When clocks go bad: neurobehavioural consequences of disrupted circadian timing. PLoS Genetics 4(5):e100040. doi:10.1371/journal.pgen.100040

    Article  CAS  Google Scholar 

  • Berra B, Rizzo AM (2009) Melatonin: circadian rhythm regulator, chronobiotic, antioxidant and beyond. Clin Dermatol 27:202–209

    Article  PubMed  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle protein–dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Buznikov GA, Lambert HW, Lauder JM (2001) Serotonin and serotonin-like substances as regulators of early embryogenesis and morphogenesis. Cell Tissue Res 305:177–186

    Article  CAS  PubMed  Google Scholar 

  • Cassone VM, Chesworth MJ, Armstrong SM (1986) Dose-dependent entrainment of rat circadian rhythms by daily injection of melatonin. J Biol Rhythms 1:219–229

    Article  CAS  PubMed  Google Scholar 

  • Cohen IR, Wise PM (1988) Age related changes in the diurnal rhythm of serotonin turnover in microdissected brain areas of estradiol-treated ovariectomized rats. Endocrinology 88:2626–2633

    Article  Google Scholar 

  • Cutrera RA, Kalsbeek A, Pevet P (1994) Specific destruction of the serotonergic afferents to the suprachiasmatic nuclei prevents triazolam-induced phase advances of hamster activity rhythms. Behav Brain Res 62:21–28

    Article  CAS  PubMed  Google Scholar 

  • Davidson AJ, Yamazaki S, Arble DM, Menaker M, Block GD (2008) Resetting of central and peripheral circadian oscillators in aged rats. Neurobiol Aging 29:471–477

    Article  PubMed  Google Scholar 

  • Garau C, Aparicio S, Rial RV, Nicolau MC, Esteban S (2006a) Age related changes in the activity-rest circadian rhythms and c-fos expression of ring doves with aging. Effects of tryptophan intake. Exp Gerontol 41:430–438

    Article  CAS  PubMed  Google Scholar 

  • Garau C, Aparicio S, Rial RV, Nicolau MC, Esteban S (2006b) Age-related changes in circadian rhythm of serotonin in ringdoves: effects of increased tryptophan ingestion. Exp Gerontol 41:40–48

    Article  CAS  PubMed  Google Scholar 

  • Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012

    Article  CAS  PubMed  Google Scholar 

  • Jagota A (2005) Aging and sleep disorders. Indian J Gerontol 19:415–424

    Google Scholar 

  • Jagota A (2006) Suprachiasmatic nucleus: the center for circadian timing system in mammals. Proc Indian Natl Sci Acad B71:275–288

    Google Scholar 

  • Jagota A, Kalyani D (2008) Daily serotonin rhythms in rat brain during postnatal development and aging. Biogerontology 9:229–234

    Article  CAS  PubMed  Google Scholar 

  • Jagota A, Reddy MY (2007) The effect of curcumin on ethanol induced changes in suprachiasmatic nucleus (SCN) and pineal. Cell Mol Neurobiol 27:997–1006

    Article  CAS  PubMed  Google Scholar 

  • Jagota A, Olcese J, Rao HN, Gupta PD (1999) Recognition of light in variable photoperiods by anophthalmic mutant rats. Brain Res 825:95–103

    Article  CAS  PubMed  Google Scholar 

  • Jagota A, de la Iglesia HO, Schwartz WJ (2000) Morning and evening circadian oscillations in the suprachiasmatic nucleus in vitro. Nat Neurosci 3:372–376

    Article  CAS  PubMed  Google Scholar 

  • Jiang ZG, Teshima K, Yang Y, Yoshioka T, Allen CN (2000) Pre- and post-synaptic actions of serotonin on rat suprachiasmatic nucleus neurons. Brain Res 866:247–256

    Article  CAS  PubMed  Google Scholar 

  • Klein DC, Moore RY, Reppert SM (eds) (1991) Suprachiasmatic nucleus: the mind’s clock. Oxford University Press, New York

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Krajnak K, Rosewell KL, Duncan MJ, Wise PM (2003) Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of the female rats. Brain Res 990:87–94

    Article  CAS  PubMed  Google Scholar 

  • Laudon M, Nir I, Zisapel N (1988) Melatonin receptors in discrete brain areas of the male rat. Impact of aging on density and on circadian rhythmicity. Neuroendocrinology 48:577–583

    Article  CAS  PubMed  Google Scholar 

  • Li H, Satinoff E (1995) Changes in circadian rhythms of body temperature and sleep in old rats. Am J Physiol Regul Integr Comp Physiol 269:R208–R214

    CAS  Google Scholar 

  • Lolova IS (1996) Morphological evidence for effects of the aging on serotonergic neurons in the rat brain stem nuclei. Acta Physiol Pharmacol Bull 22:17–25

    CAS  Google Scholar 

  • McAulay JD, Miller JP, Beck E, Nagy ZM, Pang KCH (2002) Age related disruptions in circadian timing: evidence for split activity rhythms in the SAMP8. Neurobiol Aging 23: 625–632

    Google Scholar 

  • Miguez JM, Martin FJ, Aldegunde M (1994) Effect of single doses and daily melatonin treatments on serotonin metabolism in rat brain regions. J Pineal Res 17:170–176

    Article  CAS  PubMed  Google Scholar 

  • Mishima K, Okawa M, Shimizu T, Hishikawa Y (2001) Diminished melatonin secretion in the elderly caused by insufficient environmental illumination. J Clin Endocrinol Metab 86:129–134

    Article  CAS  PubMed  Google Scholar 

  • Monk TH, Buysse DJ, Reynolds CF, Kupfer DJ, Hock PR (1995) Circadian temperature rhythms of older people. Exp Gerontol 30:455–474

    Article  CAS  PubMed  Google Scholar 

  • Morin LP (1999) Serotonin and the regulation of mammalian circadian rhythmicity. Ann Med 31:12–33

    Article  CAS  PubMed  Google Scholar 

  • Nygard M, Palomba M (2006) The GABAergic network in the suprachiasmatic nucleus as a key regulator of the biological clock: does it change during senescence? Chronobiol Int 23:427–435

    Article  CAS  PubMed  Google Scholar 

  • Pazo D, Cardinali DP, Cano P, Reyes Toso CA, Esquifino AI (2002) Age-related changes in 24-hour rhythms of norepinephrine content and serotonin turnover in rat pineal gland: effect of melatonin treatment. Neurosignals 11:81–87

    Article  CAS  PubMed  Google Scholar 

  • Petkov VD, Stancheva SL, Petkov VV, Alova LG (1987) Age related changes in brain biogenic monoamines and monoamine oxidase. Gen Pharmacol 18:397–401

    CAS  PubMed  Google Scholar 

  • Revell VL, Burgess HJ, Gazda CJ, Smith MR, Fogg LF, Eastman CI (2006) Advancing human circadian rhythms with afternoon melatonin and morning intermittent bright light. J Clin Endocrinol Metab 91:54–59

    Article  CAS  PubMed  Google Scholar 

  • Sack R, Lewy A, Hughes R (1998) Use of melatonin for sleep and circadian rhythm disorders. Ann Med 30:115–121

    Article  CAS  PubMed  Google Scholar 

  • Sadki A, Bentivoglio M, Kristensson K, Nygard M (2007) Suppressors, receptors and effects of cytokines on the aging mouse biological clock. Neurobiol Aging 28:296–305

    Article  CAS  PubMed  Google Scholar 

  • Śanchez S, Śanchez C, Paredes SD, Cubero J, Rodriguez AB, Barriga C (2008) Circadian variations of serotonin in plasma and different brain regions of rats. Mol Cell Biochem 317:105–111

    Article  PubMed  CAS  Google Scholar 

  • Scarbrough K, Losse-Olsen S, Wallen EP, Turek FW (1997) Aging and photoperiod affect entrainment and quantitative aspects of locomotor behavior in Syrian hamsters. Am J Physiol 272:R1219–R1225

    CAS  PubMed  Google Scholar 

  • Seebart BR, Stoffel RT, Behan M (2007) Age-related changes in the serotonin 2A receptor in the hypoglossal nucleus of male and female rats. Respir Physiol Neurobiol. 158:14– 21

    Google Scholar 

  • Sharman EH, Bondy SC, Sharman KG, Lahri D, Cotman CW, Perreau VM (2007) Effects of melatonin and age on gene expression in mouse CNS using microarray analysis. Neurochem Int 50:336–344

    Article  CAS  PubMed  Google Scholar 

  • Sibille E, Su J, Leman S, Guisquet AM, Ibarguen-Vargas Y, Joeyen-Waldorf J, Glorioso C, Tseng GC, Pezzone M, Hen R, Belzung C (2007) Lack of serotonin1B receptor expression leads to age related motor dysfunction, early onset of brain molecular aging and reduced longevity. Mol Psychiatry 12:1042–1075

    Article  CAS  PubMed  Google Scholar 

  • Slotkin TA, Cousins MM, Tate CA, Seidler FJ (2005) Serotonergic cell signaling in animal model of aging and depression; olfactory bulbectomy elicits different adaptations in brain regions of young adult vs aging rats. Neuropsychopharmacology 30:52–57

    Article  PubMed  Google Scholar 

  • Smith RG, Betancourt L, Sun Y (2005) Molecular endocrinology and physiology of the ageing central nervous system. Endocr Rev 26:203–250

    Article  CAS  PubMed  Google Scholar 

  • Stehle JH, von Gall C, Korf HW (2003) Melatonin: a clock-output, a clock-input. J Neuroendocrinol 15:383–389

    Article  CAS  PubMed  Google Scholar 

  • Sun X, Deng J, Liu T, Borjigin J (2002a) Circadian 5-HT production regulated by adrenergic signaling. Proc Natl Acad Sci USA 99:4686–4691

    Article  CAS  PubMed  Google Scholar 

  • Sun X, Deng J, Liu T, Borjigin J (2002b) Circadian 5-HT production regulated by adrenergic signaling. Proc Natl Acad Sci USA 99:4686–4691

    Article  CAS  PubMed  Google Scholar 

  • Tang JP, Melethil S (1995) Effect of aging on the kinetics of blood–brain barrier uptake of tryptophan in rats. Pharm Res 12:1085–1091

    Article  CAS  PubMed  Google Scholar 

  • Timiras PS, Hudson DB, Segall PE (1984) Life time brain serotonin: regional effects of age and precursor availability. Neurobiol Aging 5:235–242

    Article  CAS  PubMed  Google Scholar 

  • Touitou Y (2001) Human aging and melatonin. Clinical relevance. Exp Gerontol 36:1083–1100

    Article  CAS  PubMed  Google Scholar 

  • Toussaint O, Dumont P, Dierick JF, Pascal T, Frippiat C, Chainiaux F, Sluse F, Eliaers F, Remacle J (2000) Stress-induced premature senescence. Essence of life, evolution, stress, and aging. Ann NY Acad Sci 908:85–98

    Article  CAS  PubMed  Google Scholar 

  • Turek FW, Penev P, Zhang Y, van Reeth O, Zee P (1995) Effects of age on the circadian system. Neurosci Biobehav Rev 19:53–58

    Article  CAS  PubMed  Google Scholar 

  • Varcoe TJ, Kennaway DJ, Voultsios A (2003) Activation of 5-HT2C receptors acutely induces Per gene expression in the rat suprachiasmatic nucleus at night. Mol Br Res 119:192–200

    Google Scholar 

  • von Gall C, Weaver DR (2008) Loss of responsiveness to melatonin in aging mouse suprachiasmatic nucleus. Neurobiol Aging 29:464–470

    Article  CAS  Google Scholar 

  • Weinert D (2005) The temporal order of mammals. Evidence for multiple central and peripheral control mechanisms and for endogenous and exogenous components: some implications for research on aging. Biol Rhythm Res 36:293–308

    Article  Google Scholar 

  • Weinert H, Weinert D (1998) Circadian activity rhythms of laboratory mice during the last weeks of their life. Biol Rhythm Res 29:159–178

    Article  Google Scholar 

  • Witting W, Mirmiran M, Boss NPA, Swaab DF (1993) Effect of light intensity on diurnal sleep-wake distribution in young and old rats. Brain Res Bull 30:157–162

    Article  CAS  PubMed  Google Scholar 

  • Wu YH, Zhou JN, Yan Heerikhuize J, Joclaus R, Swaab DF (2007) Decreased MT, Melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer’s diseases. Neurobiol Aging 28:1239–1247

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by UGC (Ref: F. No: 32-613/2006 (SR)), DST (Do No: SR/SO/AS-47/2004) and ICMR (Ref. No. BMS/NTF/14/2006-2007) grants to A. J. CSIR fellowship to D. Kalyani is acknowledged. Authors are thankful to Prof. W. J. Schwartz for critical reading and valuable suggestions during preparation of this manuscript.

Author information

Authors and Affiliations

  1. Neurobiology and Molecular Chronobiology Laboratory, Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India

    Anita Jagota & D. Kalyani

Authors
  1. Anita Jagota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Kalyani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anita Jagota.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jagota, A., Kalyani, D. Effect of melatonin on age induced changes in daily serotonin rhythms in suprachiasmatic nucleus of male Wistar rat. Biogerontology 11, 299–308 (2010). https://doi.org/10.1007/s10522-009-9248-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-009-9248-9

Keywords

Search

Navigation