Cellular and Molecular Neurobiology

, Volume 28, Issue 3, pp 331–342 | Cite as

Stress Upregulates TPH1 but not TPH2 mRNA in the Rat Dorsal Raphe Nucleus: Identification of Two TPH2 mRNA Splice Variants

  • Nashat Abumaria
  • Adema Ribic
  • Christoph Anacker
  • Eberhard Fuchs
  • Gabriele Flügge
Original Paper

Abstract

Serotonin is implicated in stress-related psychopathologies. Two isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, TPH1 and TPH2, are known. We show here that in the rat dorsal raphe nucleus (DRN), the nucleus that contains the highest number of 5-HT neurons in the brain, TPH1 mRNA reveals a low level of expression but is detectable both by quantitative real-time PCR and in situ hybridization whereas in the pineal gland (PiG), TPH1 mRNA is strongly expressed. To examine effects of stress on TPH expression we exposed male Wistar rats to daily restraint stress for 1 week. As shown by quantitative real-time PCR, TPH1 mRNA is 2.5-fold upregulated by the stress in DRN but not in PiG. Using 3′-RACE, we identified two TPH2 mRNA splice variants in the rat DRN which differ in the length of their 3′-untranslated regions (UTRs). TPH2b (with a short 3′-UTR) is the predominant variant in the DRN, whereas TPH2a (with a longer 3′-UTR) shows a low abundance in this nucleus. In the PiG, only TPH2b is detectable revealing a low level of expression. Expression of both TPH2 splice variants is not affected by stress, neither in DRN nor in the PiG. These data indicate that TPH1 in the serotonergic neurons of the DRN might be relevant for stress-induced psychopathologies.

Keywords

Serotonin Tryptophan hydroxylase Splice variant Stress Affective disorders Pineal gland 

Abbreviations

3′-RACE

3′-Rapid amplification of cDNA ends

5-HT

5-hydroxytryptamine or serotonin

DRN

Dorsal raphe nucleus

PiG

Pineal gland

RT

Room temperature

TPH

Tryptophan hydroxylase

UTR

Untranslated region

Notes

Acknowledgments

Nashat Abumaria was in part funded by the DFG-Research Center Molecular Physiology of the Brain (CMPB) at the University of Göttingen. Adema Ribic is supported by a European Community fellowship for Neuroscience Early Stage Research Training (NEUREST), Göttingen, and is enrolled in the MSc/PhD Program for Molecular Biology at the University of Göttingen. Christoph Anacker is a fellow and grant recipient of the MSc/PhD Program Neurosciences at the University of Göttingen. We are grateful to Dr. B. Czeh for helpful discussions and to the excellent technical assistance of A. Hoffmann.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Nashat Abumaria
    • 1
    • 2
  • Adema Ribic
    • 1
    • 3
  • Christoph Anacker
    • 4
  • Eberhard Fuchs
    • 1
    • 5
    • 6
  • Gabriele Flügge
    • 1
    • 5
  1. 1.Clinical Neurobiology Laboratory, German Primate CenterLeibniz Institute for Primate ResearchGöttingenGermany
  2. 2.Center for Learning and Memory, School of Medicine B.303Tsinghua UniversityBeijingChina
  3. 3.Department of Primate GeneticsGerman Primate CenterGöttingenGermany
  4. 4.International Master’s/PhD Program NeurosciencesUniversity of GöttingenGöttingenGermany
  5. 5.DFG Research Center for the Molecular Physiology of the BrainGöttingenGermany
  6. 6.Department of Neurology, University Medical CenterUniversity of GöttingenGöttingenGermany

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