Photoperiod regulates the daily profiles of Tryptophan Hydroxylase-2 gene expression the raphe nuclei of rats

Main Article Content

Louay Labban
Zeina Malek


Tryptophan hydroxylase-2 mRNA (TPH, the rate limiting enzyme in 5-HT synthesis) expression levels display circadian variations in the median and dorsal raphe nuclei. This circadian pattern is under the control of the suprachiasmatic nuclei (SCN), the master clock. Photoperiodic cue is encoded by the SCN which convey the seasonal message to target sites. In the present study, we have investigated the effect of photoperiodic changes on the serotonergic neurones of the raphe nuclei. We have assessed the daily expression of TPH2 mRNA in both median and dorsal raphe nuclei of rats housed either under long photoperiod (18 h light/6 h dark cycle, LP18:6) or short photoperiod (SP6:18). Our results demonstrate that under LP18:6, TPH2 mRNA levels display a progressive decrease during the dark period and a maximal expression is reported at the beginning of the light period. The expression pattern of TPH2 mRNA under SP6:18 remains unchanged during the dark period and increases significantly before the day/night transition. This latter expression pattern is in line with the daily profiles of TPH2 mRNA reported previously under standard lighting regimen (12 h light/12 h dark cycle). The present results suggest that TPH2 mRNA expression pattern within DR and MR is affected by photoperiod which might in turn affect TPH content and 5­HT release within the circadian structures, but also in all the serotonergic projection areas of the brain.

  • Tryptophan hydroxylase-2; suprachiasmatic nuclei; Photoperiodic cue; mRNA

Article Details

How to Cite
Labban, L., & Malek, Z. (2020). Photoperiod regulates the daily profiles of Tryptophan Hydroxylase-2 gene expression the raphe nuclei of rats. International Journal of Current Research in Physiology and Pharmacology (IJCRPP), 4(1), 1-5.


1- Charles M. Morin et al. 1994. Behavioral and Pharmacological Therapies for Late-Life InsomniaA Randomized Controlled Trial. JAMA. 1999;281(11):991-999. doi:10.1001/jama.281.11.991
2- Yannielli PC, Brewer JM, Harrington ME. Blockade of the NPY Y5 receptor potentiates circadian responses to light: complementary in vivo and in vitro studies. Eur J Neurosci. 2004 Feb;19(4):891-7.
3- Meyer-Bernstein EL, Morin LP. Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J Neurosci. 1996 Mar 15;16(6):2097-111.
4- Hay-Schmidt et al. Projections from the raphe nuclei to the suprachiasmatic nucleus of the rat. Journal of Chemical Neuroanatomy Volume 25, Issue 4, July 2003, Pages 293-310
5- Barassin, Stéphane & Raison, Sylvie & Saboureau, Michel & Bienvenu, Christèle & Maitre, Michel & Malan, André & Pevet, Paul. (2002). Circadian tryptophan hydroxylase levels and serotonin release in the suprachiasmatic nucleus of the rat. The European journal of neuroscience. 15. 833-40. 10.1046/j.1460-9568.2002.01928.x.
6- Malek Z.,S., Pevet P. and Raison S. Circadian changes in Tryptophan Hydroxylase protein levels within the Rat Intergeniculate Leaflets and Raphe Nuclei. Neuroscience 2004 125 (3) 749–758.
7- Malek et al., 2005. Tissue‐specific expression of tryptophan hydroxylase mRNAs in the rat midbrain: anatomical evidence and daily profiles European Journal of Neurosciences. . Volume22, Issue4. Pages 895-901.August 2005.
8- Zeina S. Malek, Dominique Sage, Paul Pévet, Sylvie Raison, Daily Rhythm of Tryptophan Hydroxylase-2 Messenger Ribonucleic Acid within Raphe Neurons Is Induced by Corticoid Daily Surge and Modulated by Enhanced Locomotor Activity, Endocrinology, Volume 148, Issue 11, 1 November 2007, Pages 5165–5172,
9- Glass et al. Serotonin Modulates Photic Responses in the Hamster Suprachiasmatic Nuclei .The Journal of Neuroscience, June 1994, 74(6): 3635-3642
10- Dudley TE, DiNardo LA, Glass JD. Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurosci. 1998 Jul 1;18(13):5045-52
11- Grossman et al. Human T Regulatory Cells Can Usethe Perforin Pathway to CauseAutologous Target Cell Death Immunity, October, 2004. Vol. 21, 589–601,
12- Mrugala et al. Rhythmic multiunit neural activity in slices of hamstersuprachiasmatic nucleus reflect prior photoperiod. Am J Physiol Regulatory Integrative Comp Physiol278: R987–R994, 2000.
13- Vanderleest et al., 2007. Seasonal encoding by the circadian pacemaker of the SCN .Curr Biol. 2007 Mar 6;17(5):468-73. Epub 2007 Feb 22.
14- Sumová, Alena & Bendová, Zdenka & Peters, R & Schwartz, W & Illnerová, Helena. (1995). The rat suprachiasmatic nucleus is a clock for all seasons. Proceedings of the National Academy of Sciences of the United States of America. 92. 7754-8. 10.1073/pnas.92.17.7754.
15- Tournier et al., 2003. Photoperiod differentially regulates clock genes’ expression in the suprachiasmatic nucleus of Syrian hamster. Neuroscience Volume 118, Issue 2, 8 May 2003, Pages 317-322
16- Johnston JD, Ebling FJ, Hazlerigg DG. Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and pars tuberalis of the Siberian hamster (Phodopus sungorus).Eur J Neurosci. 2005 Jun;21(11):2967-74.
17- Oster et al., 2017 . Interaction between circadian rhythms and stress. Neurobiology of Stress 6 (2017) 57-67
18- Bering T, Hertz H, Rath MF. Rhythmic release of corticosterone induces circadian clock gene expression in the cerebellum. Neuroendocrinology. 2019 Sep 27. doi: 10.1159/000503720
19- Simonneaux, V. and Ribelayga, C. 2003. Generation of the melatonin endocrine message in mammals: a review of the complex regulation of melatonin synthesis by norepinephrine, peptides, and other pineal transmitters. Pharmacol Rev. 2003 Jun;55(2):325-95.
20- Ahlersova et al., 1992. Influence of light regimen and time of year on circadian oscillations of insulin and corticosterone in rats. Physiological research / Academia Scientiarum Bohemoslovaca 41(4):307-14 • February 1992.
21- Illnerova et al., 1986. Illnerova H, Hoffman K, and Vanecek J (1986) Adjustment ofthe rat pineal Nacetyltransferase rhythm to change fromlong to short photoperiod depends on the direction of theextension of the dark period. Brain Res 362:403-408.
22- Ribelayga et al., 1999. The Circadian Clock in the Retina Controls Rod-Cone Coupling. Neuron 59(5):790-801 •
23- Shen & Semba, 1994 . A direct retinal projection to the dorsal raphe nucleus in the rat. Brain Res. 1994 Jan 28;635(1-2):159-68.
24- Fite et al., 1999. Fite KV, Janusonis S, Foote W, Bengston L (1999) Retinal afferents tothe dorsal raphe nucleus in rats and Mongolian gerbils. J CompNeurol 414:469–484.
25- Pinato et al., 2004. Bimodal Daily Variation in the Serotonin Content in theRaphe Nuclei of Rats. Biological Rhythm Research0165-0424/2300-000$16.002004,
26- Messager et al., 1999. Decoding photoperiodic time through Per1 and ICER gene amplitude. PNAS August 17, 1999 96 (17) 9938-9943;
27- Dardente et al., 2003. Melatonin inducesCry1expression in the pars tuberalis of the rat. Molecular Brain Research 114 (2003) 101–106.
28- Johnston JD1, Tournier BB, Andersson H, Masson-Pévet M, Lincoln GA, Hazlerigg DG. Multiple effects of melatonin on rhythmic clock gene expression in the mammalian pars tuberalis. Endocrinology. 2006 Feb;147(2):959-65. Epub 2005 Nov 3.
29- Wagner GC, Johnston JD, Tournier BB, Ebling FJ, Hazlerigg DG. Melatonin induces gene-specific effects on rhythmic mRNA expression in the pars tuberalis of the Siberian hamster (Phodopus sungorus). Eur J Neurosci. 2007 Jan;25(2):485-90.
30- Masson-Pevet et al., 1994. Daily variations in melatonin receptor density of rat pars tuberalis and suprachiasmatic nuclei are distinctly regulated. Brain Research Volume 641, Issue 1, 28 March 1994, Pages 92-98.
31- Miguez et al., 1996. Daily and Photoperiodic Melatonin Binding Changes in the Suprachiasmatic Nuclei, Paraventricular Thalamic Nuclei, and Pars Tuberalis of the Female Siberian Hamster (Phodopus sungorus). JOURNAL OF BIOLOGICAL RHYTHMS, Vol. 11 No. 4, December. 325-332.